Per Minor Magnus

• Grefslie, Marianne Rørholt; Håberg, Siri Eldevik; Magnus, Maria Christine; Omsland, Tone Kristin & Magnus, Per Minor (2026). Parental asthma and childhood asthma phenotypes: maternal associations with persistent asthma. BMJ Open Respiratory Research. 13(1). doi: 10.1136/bmjresp-2026-004245. Full text in Research Archive Show summary

  Background: Maternal asthma has been more strongly associated with asthma in offspring than paternal asthma, but the influence of parental asthma on distinct asthma phenotypes remains unclear. Methods: We studied 16 055 children from the Norwegian Mother, Father and Child Cohort Study (MoBa). Parental asthma was reported at recruitment and classified as no parental asthma (reference), maternal asthma only, paternal asthma only or both parents with asthma. Offspring asthma was assessed at ages 3, 7 and 14 years through questionnaire-based parental reports, and four phenotypes were defined: never asthma, early-onset transient, early-onset persistent and late-onset asthma. Logistic regression was used to estimate associations between parental asthma status and offspring phenotypes, adjusting for sociodemographic, lifestyle and atopic factors, including atopic eczema and pollen/hay fever. Results: Offspring asthma phenotypes were distributed as follows: never asthma 88.8%, early-onset transient asthma 3.3%, early-onset persistent asthma 2.7% and late-onset asthma 5.2%. Maternal asthma was associated with increased odds of all offspring asthma phenotypes: early-onset transient asthma (OR 2.09, 95% CI 1.52 to 2.88), early-onset persistent asthma (OR 3.47, 95% CI 2.56 to 4.71) and late-onset asthma (OR 2.18, 95% CI 1.69 to 2.81). Paternal asthma showed similar associations, although point estimates were generally smaller: early-onset transient asthma (OR 2.01, 95% CI 1.48 to 2.73), early-onset persistent asthma (OR 2.49, 95% CI 1.81 to 3.44) and late-onset asthma (OR 1.85, 95% CI 1.44 to 2.38). Asthma in both parents was most strongly associated with early-onset persistent asthma (OR 5.34, 95% CI 2.86 to 9.98), whereas associations with early-onset transient and late-onset asthma were smaller and accompanied by wider CIs. The overall pattern of associations was similar across analyses stratified by parental atopy. Conclusions: Associations with maternal asthma were more pronounced than those with paternal asthma, particularly for early-onset persistent and late-onset phenotypes, although CIs overlapped for most comparisons. In contrast, early-onset transient asthma showed less differentiation by parental asthma status.

• Quinn, Liam; Caspersen, Ida Henriette; Magnúsdóttir, Ingibjörg; Wang, Yue; Lundberg, Mischa & Gådin, Jesper [Show all 38 contributors for this article] (2026). The role of genetic liability for psychiatric disorders and personality traits in post covid syndrome: data from three Nordic population cohorts. EClinicalMedicine. 95. doi: 10.1016/j.eclinm.2026.103928. Full text in Research Archive
• Chen, Su; Lee, Yunsung; Håberg, Siri Eldevik; Magnus, Per Minor; Page, Christian Magnus & Kovács, Emese H.C. [Show all 12 contributors for this article] (2026). Epigenome-Wide DNA Methylation Levels During Pregnancy: Associations with Parity Across Diverse Populations. Epigenomes. ISSN 2075-4655. 10(2), p. 30–30. doi: 10.3390/epigenomes10020030. Full text in Research Archive Show summary

  Background/Objectives: Parity, the number of times a woman carries a pregnancy to viability, has been linked to long-term maternal health outcomes. The mechanisms linking parity to health outcomes are poorly understood but may reflect influences of pregnancy on the maternal epigenome. Methods: This study examines the relationship between parity and DNA methylation (DNAm) during pregnancy using data from three cohorts: the Norwegian Mother, Father and Child Cohort Study (MoBa), the Atlanta African American Maternal-Child (AAAMC) cohort, and the Isle of Wight (IOW) Birth Cohort. Results: An epigenome-wide association study (EWAS) in MoBa identified 5374 cytosine–phosphate–guanine sites (CpGs) that were statistically significantly associated with parity, of which 69% were positively and 31% negatively correlated. Replication analyses confirmed 3491 CpGs in at least one cohort, and 93 CpGs in both AAAMC and IOW. Gene enrichment analysis revealed significant involvement of developmental and signaling pathways, including calcium signaling and neuroactive ligand–receptor interaction. Additionally, 584 differentially methylated regions (DMRs) were detected, with 90% overlapping individual parity-related CpGs. Conclusions: These findings suggest that parity influences epigenetic patterns, potentially affecting biological processes and molecular functions relevant to maternal health later in life.

• Corfield, Elizabeth Claire; Shadrin, Alexey; Frei, Oleksandr; Rahman, Mohammad Zillur; Akdeniz, Bayram Cevdet & Filiz, Tahir Tekin [Show all 29 contributors for this article] (2026). Family genetic designs in MoBa provide insights into health and functioning. Nature. ISSN 0028-0836. doi: 10.1038/s41586-026-10926-5. Full text in Research Archive Show summary

  Genome-wide association studies using large, population-based samples of unrelated individuals have discovered thousands of genetic associations with health and disease1. These studies can help explain genetic and environmental risks. However, increasing evidence suggests that population-based estimates, while precise, can also reflect confounding that affects their use and interpretation. This confounding can be overcome using data from genotyped family members, such as nuclear mother–father–child trios2,3. However, samples of genotyped families are rare4,5,6,7,8,9,10,11. Here we illustrate some of the advantages of familial data using the Norwegian Mother, Father and Child Cohort Study (MoBa), a population-based cohort of parents and offspring with extensive genotype data (n ≈ 230,000) (ref. 3), along with broad and longitudinal phenotyping of health and functioning. We provide an overview of MoBa and describe the quality control of genotype data tailored to this extensively related sample. We then use trio data to illustrate how family-based genomic designs can identify distinct direct and indirect sources of genetic influence and structural confounding. As examples, we analyse children’s height, educational achievement, depressive symptoms and sleep duration. These demonstrations highlight MoBa as a broadly valuable resource for advancing understanding of health and functioning across the lifecourse and generations.

• Karachaliou, Marianna; Kogevinas, Manolis; Smith, George Davey; Andersen, Anne Marie Nybo; Avraam, Demetris & Barros, Henrique [Show all 30 contributors for this article] (2026). Early-life infections and life course health and disease in the EU child cohort network. European Journal of Epidemiology (EJE). ISSN 0393-2990. doi: 10.1007/s10654-026-01451-w. Full text in Research Archive
• Dalgeir, Anne Mari; Caspersen, Ida Henriette; Caronna, Edoardo; Magnus, Per Minor; Trogstad, Lill-Iren Schou & Bjørk, Marte-Helene (2026). The Association of Headache and Physical Activity in Times of the COVID-19 Pandemic: A Prospective Cohort Study. Brain and Behavior. 16(7). doi: 10.1002/brb3.71490. Full text in Research Archive Show summary

  Background: Prospective studies of the risk of headache with low levels of physical activity are limited. Pandemic-related lifestyle changes and the potential headache risk associated with Coronavirus Disease (COVID-19) and SARS-CoV-2 vaccination may complicate this association. Our study aims to investigate the potential risk of new bothersome headache in relation to physical activity and explore the impact of COVID-19 and SARS-CoV-2 vaccines on this association. Methods: This prospective cohort study utilized questionnaires from the Norwegian Mother, Father, and Child Cohort Study (MoBa). Logistic regression analyses were conducted to estimate the adjusted odds ratio (aOR) for new-onset headache according to physical activity levels. Models were adjusted for gender, age, body mass index, education level, smoking, alcohol intake, anxiety/depression, and COVID-19 and SARS-CoV-2 vaccination prior to February 2022. The potential impact of COVID-19 disease was investigated in a stratified analysis. Results: Both low level of physical activity and inactivity were significantly associated with new bothersome headache when compared to moderate to high activity levels (low activity: aOR 1.22, 95% CI 1.13 to 1.30; inactive: aOR 1.26, 95% CI 1.05 to 1.51). The corresponding adjusted absolute risk differences were 1.9% (95% CI 1.2 to 2.6) and 2.3% (95% CI 0.4 to 4.3), respectively. Findings persisted across COVID-19 status strata, without significant interactions. Conclusion: Our findings underscore the potential role of physical activity in mitigating new bothersome headache also for headache associated with COVID-19. Encouraging regular physical activity may serve as a preventive measure for headache in a pandemic setting.

• Reme, Bjørn-Atle; Magnus, Per; Håberg, Siri Eldevik & Kinge, Jonas Minet (2026). General practitioner utilization by age, sex and disease in Norway from 2012–2023: a national health registry study. Scandinavian Journal of Primary Health Care. ISSN 0281-3432. 44(1). doi: 10.1080/02813432.2026.2666623. Full text in Research Archive Show summary

  Objective: To describe trends in the number of general practitioner consultations in primary care, stratified by age, sex, and diagnosis. Method: Register-based population-wide repeated cross-sectional study. Data from the Norwegian Control and Distribution of Health Reimbursement (KUHR) database, linked to data from the Norwegian Population Registry. Participants: All Norwegians alive and living in the country each year from 2012 to 2023. The population grew from 4,985,870 in 2012 to 5,488,984 persons in 2023 during this period. Main outcome measure: The average annual number of general practitioner consultations per inhabitant in primary healthcare. Results: The average number of yearly General Practitioner (GP) visits per inhabitant increased from 3.1 to 3.6 for women and from 2.2 to 2.4 for men from 2012 to 2023. Age-specific utilization trends revealed the largest increase among 16–19-year-old women, whose GP visits rose from 2.05 to 2.99 per year. Diagnosis-specific trends highlighted a substantial increase in consultations for mental illness among women, from 0.31 to 0.46 per inhabitant, with the largest relative growth among 6–15-year-old girls (+139%). Conversely, consultations for heart disease saw the largest relative decline, particularly among women aged 67 to 79 (−68.3%) and men aged 80 to 89 (−0.94 consultations per inhabitant). Conclusions: Primary care utilization has increased over the past decade, with notable variation by age, sex, and diagnosis. The particularly strong increase in consultations for mental illness among young individuals highlight the potential for considering other medical professionals, such as specially trained nurses, to serve as the primary point of contact for young individuals with mental health challenges.

• Fejzo, Marlena; Wang, Xinran; Tan, Qing; Zöllner, Julia; Pujol-Gualdo, Natàlia & Laisk, Triin [Show all 101 contributors for this article] (2026). Multi-ancestry genome-wide association study of severe pregnancy nausea and vomiting. Nature Genetics. ISSN 1061-4036. 58(4), p. 810–820. doi: 10.1038/s41588-026-02564-4. Full text in Research Archive
• Caspersen, Ida Henriette; Hernáez, Álvaro; Peña, Sebastián; Shaaban, Ahmed Nabil; Magnus, Maria Christine & Karvonen, Sakari [Show all 8 contributors for this article] (2026). Cigarette smoking and SARS-CoV-2 infection: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study. BMC Infectious Diseases. 26(1). doi: 10.1186/s12879-026-12750-8. Full text in Research Archive
• Bohlin, Jon; Lee, Yunsung; Caspersen, Ida Henriette; Robertson, Anna Hayman; Page, Christian Magnus & Gjessing, Håkon Kristian [Show all 10 contributors for this article] (2026). Longitudinal study of genome-wide DNA methylation in individuals with and without post-acute symptoms following SARS-CoV-2 infection. Epigenomics. ISSN 1750-1911. 18(4), p. 411–419. doi: 10.1080/17501911.2026.2656361. Full text in Research Archive Show summary

  Background: Symptoms following SARS-CoV-2 infection, referred to as Long-COVID, have been reported since the pandemic. We investigated whether COVID-19 or Long-COVID is associated with persistent genome-wide DNA methylation (DNAm) changes in whole blood using a longitudinal design. Methods: DNAm was measured using the Illumina EPIC V2 platform (859,651 CpGs) in 297 adult participants (594 samples in total) from two Norwegian population-based cohorts, with samples collected pre-infection (2020) and during the pandemic (2023). Participants were classified as Long-COVID, COVID-19 (no persistent symptoms), or not infected. Results: No significant DNAm differences were observed between Long-COVID and not infected at either time point (p = 0.745(FDR)) or during the pandemic specifically (p = 0.629(FDR)). Likewise, no differences were detected between COVID-19 and not infected across both time points (p = 0.883(FDR)) or during the pandemic (p = 0.287(FDR)). Sex-stratified analyses of the X chromosome revealed no significant DNAm differences for Long-COVID or COVID-19 in males (both p = 0.999(FDR)) or females (both p = 0.999(FDR)). Epigenetic age acceleration was also evaluated using DunedinPACE (DP) and PhenoAge (PA), but no significant differences were detected for Long-COVID (p = 0.695 [DP], p = 0.528 [PA]) or COVID-19 (p = 0.624 [DP], p = 0.348 [PA]). Conclusion: No persistent epigenetic age- or DNAm based differences due to Long-COVID or SARS-CoV-2 infection were detected in our cohorts.

• Robertson, Anna Hayman; Wolf, Asia-Sophia Fumika Michaela; Fossum, Even; Solum, Guri; Bhandari, Sabin & Vikse, Elisabeth Lea [Show all 12 contributors for this article] (2026). Long-lasting cross-reactive and polyfunctional SARS-CoV-2 T cell responses in seniors are maintained after repeated vaccination and infections. Vaccine. ISSN 0264-410X. 80, p. 1–12. doi: 10.1016/j.vaccine.2026.128511. Full text in Research Archive
• Trinh, Nhung; Rostami, Sina; Pedroncelli, Michele; Cheesman, Rosa Catherine Gillespie; Magnus, Per Minor & Johansson, Stefan [Show all 8 contributors for this article] (2026). Prenatal antidepressant use and longitudinal differences in BMI up to 8 years of age in the offspring born to mothers with depression/anxiety in the Norwegian Mother, Father and Child Cohort Study. Journal of Affective Disorders. ISSN 0165-0327. 405. doi: 10.1016/j.jad.2026.121552. Full text in Research Archive Show summary

  Background: No study has explored how prenatal antidepressant exposure affects offspring body mass index (BMI) throughout childhood. Methods: We used data from the Norwegian Mother, Father, and Child Cohort Study (MoBa) linked to the Medical Birth Registry of Norway and the MoBa Genetics. We included 6084 pregnancy-child dyads (singleton, liveborn) with child BMI data up to 8 years, born to women with pre-pregnancy depression/anxiety. Prenatal antidepressant exposure groups include continued antidepressants in pregnancy (n = 626), discontinued antidepressants proximal to pregnancy (n = 412), or unexposed to antidepressants (n = 5046). Mean BMI differences over time between groups were calculated using multilevel mixed-effect linear models. Results: Children born to continuers had comparable childhood BMIs with those born to unexposed mothers or mothers who discontinued antidepressant, in overall and in both sexes. However, higher BMI was observed up to 3 years among male offspring of continued mothers compared to discontinuers in those exposed to selective-serotonin-reuptake-inhibitor before pregnancy (β = 0.334; 95% CI: 0.081 to 0.588 at baseline). Lower BMI was seen among female offspring born to continued vs. discontinued mothers with larger gap over time, especially between low-moderate use of antidepressant vs. discontinuation during pregnancy. Analyses integrating parental genetic liability for depression, BMI, and antidepressant response using polygenic risk scores in (n = 1913) suggests potential influence of the genetic component on the longitudinal differences in BMI in some strata. Conclusion: The childhood BMI of children born to mothers with pre-pregnancy depression/anxiety did not differ across prenatal antidepressant trajectories. Exploratory analyses revealed differences at specific timeframes which are sex-specific and potentially influenced by genetic liability profiles.

• Grindstad, Thea Karoline Walstad; Magnus, Maria Christine; Nallo, Alessandro Di; Ramlau-Hansen, Cecilia Høst; Liew, Zeyan & Hanevik, Hans Ivar [Show all 13 contributors for this article] (2026). Per- and polyfluoroalkyl substances (PFAS) and miscarriage: The Norwegian Mother, Father and Child Cohort study. Environmental Research. ISSN 0013-9351. 298. doi: 10.1016/j.envres.2026.124276. Full text in Research Archive Show summary

  Background Miscarriage is prevalent, occurring in around 15% of recognized pregnancies. Yet modifiable determinants remain elusive. Per- and polyfluoroalkyl substances (PFAS) can disrupt endocrine- and other biological pathways crucial for reproduction. Whether PFAS is associated with miscarriage in humans remains uncertain. Objective To examine the association between PFAS concentrations and a recent miscarriage. Methods We conducted a nested case-control study within The Norwegian Mother, Father, and Child Cohort Study (MoBa), which recruited pregnant women from 1999 to 2008. We utilized plasma concentrations of PFAS measured at enrolment from several MoBa sub-studies: Perfluorohexane sulfonate (PFHxS), Perfluoroheptane sulfonate (PFHpS), Perfluorooctane sulfonate (PFOS), Perfluorooctanoate (PFOA), Perfluorononanoate (PFNA), Perfluorodecanoate (PFDA) and Perfluoroundecanoate (PFUnDA). Associations with miscarriage were examined by comparing women with a single recent miscarriage to those with no prior pregnancies at enrollment, aiming to reduce the influence of parity on women's PFAS concentrations. Recency was defined as a miscarriage occurring within two calendar years before the MoBa child's birth. Logistic regression models, adjusted for age, education, and birth year, estimated associations between PFAS concentrations during the current pregnancy and recent miscarriage. The joint effect of the total PFAS mixture was evaluated using quantile-based g-computation. Results Among 2525 nulliparous women with mid-pregnancy PFAS measurements, 253 experienced a recent miscarriage before MoBa enrolment. No clear associations between PFAS concentrations and recent miscarriage were identified in single-pollutant models nor for the overall PFAS mixture (OR 0.95 (95 % CI: 0.83-1.09, per quartile increase in PFAS). Additional adjustments for potential confounding factors, including body mass index, menstrual cycle characteristics and use of oral contraceptives did not alter the observation of overall null-findings. Conclusions We found no clear association between PFAS concentrations and miscarriage among nulliparous women.

• Grefslie, Marianne Rørholt; Håberg, Siri Eldevik; Magnus, Maria Christine; Omsland, Tone Kristin & Magnus, Per Minor (2026). Parental asthma and risk of offspring asthma from childhood to adolescence: a population-based cohort study. BMJ Open Respiratory Research. 13(1). doi: 10.1136/bmjresp-2025-003608. Full text in Research Archive Show summary

  Background Maternal asthma has been associated with a higher risk of asthma in early childhood compared with paternal asthma, but it is unclear whether this difference persists into adolescence. Methods We analysed 55 643 children from the Norwegian Mother, Father and Child Cohort Study. Parental asthma was self-reported during pregnancy; offspring asthma was reported by mothers at ages 3, 7 and 14 years. Logistic regression models estimated associations between parental asthma and offspring asthma at each age, adjusting for maternal age, parental prepregnancy body mass index, parental education, parental smoking and parental atopic conditions, including atopic eczema and pollen/hay fever. Results Asthma prevalence among offspring was 6.5% at age 3, 5.2% at age 7 and 5.4% at age 14. Compared with children of non-asthmatic parents, adjusted ORs for asthma at age 3 were 3.11 (95% CI 2.73 to 3.54) for maternal asthma only and 2.25 (95% CI 1.97 to 2.56) for paternal asthma only. Similar patterns were observed at ages 7 (maternal OR 2.96 (95% CI 2.54 to 3.45); paternal OR 2.36 (95% CI 2.03 to 2.75)) and 14 (maternal OR 3.03 (95% CI 2.46 to 3.73); paternal OR 1.95 (95% CI 1.57 to 2.43)). At age 3, maternal asthma was associated with higher odds in boys (OR 3.30) than girls (OR 2.82), and higher absolute risk (19.2% vs 12.2%). However, interaction tests by offspring sex were not statistically significant. Conclusions Maternal asthma conferred a consistently stronger risk of offspring asthma than paternal asthma, from early childhood into adolescence. This effect appeared slightly stronger in boys in early childhood, though sex differences were not statistically significant.

• Lee, Yunsung; Gjessing, Håkon Kristian; Page, Christian Magnus; Bohlin, Jon; Lyle, Robert & Magnus, Per Minor [Show all 7 contributors for this article] (2025). Methylation differences between assisted reproductive technology-conceived and naturally conceived children near BRCA1 and NBR2. Epigenetics. ISSN 1559-2294. 20(1). doi: 10.1080/15592294.2025.2577188. Full text in Research Archive Show summary

  Recent studies have shown that newborns conceived using assisted reproductive technology (ART) exhibited significantly different DNA methylation (DNAm) profiles at birth compared to those conceived naturally. Of note was the observation of increased DNAm at the promoter region of BRCA1/NBR2 in ART-conceived newborns. However, it remains unclear if these DNAm differences persist after birth. Using the Norwegian Mother, Father, and Child Cohort Study (MoBa), a large-scale population-based pregnancy cohort with extensive longitudinal data collected through biological samples and questionnaires, we generated longitudinal DNAm data for 105 ART-conceived and 250 naturally conceived children at birth and at ages 3–22 years. DNAm differences in the BRCA1/NBR2 promoter between ART- and naturally conceived children, at birth and postnatally, were tested using linear mixed model with adjustment for maternal and newborn covariates. While ART-conceived children showed subtle hypermethylation at birth and postnatally, the differences diminished over time and did not remain statistically significant after multiple testing correction. Our findings suggest that subtle hypermethylation at the BRCA1/NBR2 promoter in ART-conceived children may represent an ART-associated epigenetic signature, although further studies in larger populations are needed to clarify its persistence and significance.

• Carson, Alexis Christine; Trinh, Nhung; Nordeng, Hedvig Marie Egeland; Liu, Xiaoqin; Munk-Olsen, Trine & Eberhard-Gran, Malin [Show all 8 contributors for this article] (2025). Initiating antidepressant treatment in pregnancy: Timing, intensity, and influential maternal and familial factors. Journal of Affective Disorders. ISSN 0165-0327. 388. doi: 10.1016/j.jad.2025.119726. Full text in Research Archive Show summary

  Objective: To describe the timing and intensity of antidepressant initiation in pregnancy using longitudinal trajectories of antidepressant prescription fills to identify associated sociodemographic, lifestyle, somatic, mental health, pregnancy, and paternal factors. Methods: This population-based cohort within the Norwegian Mother, Father and Child Cohort study linked to MoBa Genetics and the Prescribed Drug Registry included 1879 women with a new episode of self-reported depression/anxiety during pregnancy. Antidepressants were measured by week and average daily dose. Results: There were 87 initiators, from which we identified three prescription fill trajectories: Early-pregnancy initiators with rapid discontinuation (n = 41, 47.1 %), Early-pregnancy initiators with mid-pregnancy discontinuation (n = 30, 34.5 %), and Early-mid pregnancy initiators with continuation (n = 16, 18.4 %) and three dose trajectories: Low dose with discontinuation (n = 45, 51.7 %), High dose with discontinuation (n = 26, 29.9 %), and Medium dose with continuation (n = 16, 18.4 %). Thyroid disorder was associated with Early initiators with rapid discontinuation (adjusted relative risk ratios (aRRR): 4.15, 95 % CI: 1.56–11.03) compared to Unmedicated. Other psychotropics pre-pregnancy increased the likelihood of being Early initiators with mid-pregnancy discontinuation and High dose discontinuers compared to Unmedicated. Higher maternal genetic liability for depression was strongly associated with Early initiators with mid-pregnancy discontinuation (aRRR = 8.57, 95 % CI: 3.09–23.74), High dose discontinuers and Medium dose continuers across comparisons. Adverse reproductive history, immigration and alcohol pre-pregnancy emerged as important factors. Conclusions: Approximately 5 out of 100 women with a new episode of depression/anxiety initiated an antidepressant during pregnancy, predominantly in early pregnancy, with most discontinuing early to mid-pregnancy. Identified factors can be utilized by clinicians to provide personalized treatment guidance.

• Zugic, Milica; Trinh, Nhung; Rostami, Sina; Nordeng, Hedvig Marie Egeland; Ystrøm, Eivind & Bulik, Cynthia M [Show all 10 contributors for this article] (2025). Antenatal depressive and anxiety symptoms in women with eating disorders who continue or discontinue antidepressant treatment in pregnancy. Journal of Affective Disorders Reports. 22, p. 1–10. doi: 10.1016/j.jadr.2025.100985. Full text in Research Archive Show summary

  Background Limited evidence on antidepressant effectiveness in pregnant women with eating disorders (ED) challenges pharmacotherapy management. We examined antenatal depressive and anxiety symptoms with continued antidepressant use in women with ED. Methods We used data from the Norwegian Mother, Father and Child Cohort Study (MoBa) linked to the Medical Birth Registry of Norway and MoBa Genetics. MoBa questionnaires at weeks 17 (early) and 30 (mid-late pregnancy) measured antidepressant exposure and symptoms of depression and anxiety using the 5-item Hopkins Symptom Checklist. We fitted generalised linear models and adjusted for confounding. In a subsample, we stratified analyses by polygenic-score tertiles for antidepressant response. Results We identified 5920 pregnancies in women with ED, mainly binge-eating disorder (BED) (84.0 %) and bulimia nervosa (BN) (12.4 %). Of these, 48 (0.8 %) continued antidepressants into early pregnancy, 93 (1.6 %) discontinued during, and 85 (1.4 %) discontinued before pregnancy. At early pregnancy only, continued antidepressant was associated with lower severity of depressive and anxiety symptoms relative to discontinuation. Among women with BED, this was specific to lower anxiety symptoms (β:-0.43, 95 %CI:-0.84, -0.02). This association was not observed in women with BN. In women with higher antidepressant-response polygenic-score continued antidepressant was associated with lower symptom severity relative to discontinued (range of β:-0.86 to -1.35). Conclusions Continuing antidepressants in early but not mid-late pregnancy is associated with lower severity of depressive and anxiety symptoms in women with BED. The association observed in women with higher antidepressant-response polygenic-score calls for larger studies on personalized treatment in perinatal ED.

• Dypås, Lene Brattsti; Olsen, Ann-Karin Hardie; Gützkow, Kristine Bjerve; Andreassen, Ole; Brunborg, Gunnar & Magnus, Per Minor [Show all 9 contributors for this article] (2025). Circulating MicroRNAs in Cord Blood to Predict Attention-Deficit/Hyperactivity Disorder Diagnosis. Biological Psychiatry. ISSN 0006-3223. doi: 10.1016/j.biopsych.2025.10.010. Full text in Research Archive Show summary

  Background There are large knowledge gaps in the etiology of attention-deficit/hyperactivity disorder (ADHD), and although it is a prevalent and highly heritable neurodevelopmental disorder, diagnosis can be challenging. We aimed to assess the association of circulating blood plasma microRNAs (miRNAs) at birth with ADHD for use as biomarker candidates and build an miRNA-based prediction model. Methods Our study population consisted of 206 children with ADHD (33.0% female), 207 control children (33.8% female), and their parents from the MoBa (Norwegian Mother, Father, and Child Cohort Study). Expression levels of 51 selected miRNAs in plasma from children’s cord blood at birth and from both parents during early pregnancy were quantified by quantitative polymerase chain reaction and tested for association with children’s ADHD diagnosis and ADHD symptom scores based on ratings by parents. Results Seven miRNAs were differentially expressed at birth in children with ADHD and control children (false discovery rate < .05), and 31 had a statistically significant linear relationship with parent-rated ADHD symptom score at 8 years. A 19-miRNA ADHD prediction model achieved good discrimination in the test population (area under the receiver operating curve = 0.959, accuracy = 0.893). Functional analysis for the 19-miRNA prediction set revealed involvement in several highly relevant pathways, e.g., dopaminergic synapse, circadian rhythm, and axon guidance. We also found that parental miRNA expression levels significantly associated with children’s ADHD diagnoses and/or ADHD symptoms scores. Conclusions We showed that expression levels of circulating miRNAs at birth may be used to predict increased risk of ADHD diagnosis, and our 19-miRNA set should be included in future efforts to develop a biomarker panel.

• Blix, Kristine; Laake, Ida; Caspersen, Ida Henriette; Feiring, Berit; Robertson, Anna Hayman & Skodvin, Siri Nærland [Show all 11 contributors for this article] (2025). New‐Onset Headache After SARS-CoV‐2 Infection and Vaccination: Results From Three Population‐Based Cohorts in Norway. European Journal of Neurology. ISSN 1351-5101. 32(12). doi: 10.1111/ene.70437. Full text in Research Archive Show summary

  ABSTRACT Background Persistent headache after SARS‐CoV‐2 infections and vaccination has been reported. However, limited data exist on the risk of new‐onset headache after these exposures compared to unexposed periods in the general population. Methods We used data from three population‐based cohorts ( N  = 85,774, age 19–81 years). SARS‐CoV‐2 infections and vaccinations were obtained from national registries and questionnaires. Before and after Omicron emergence, participants stated whether they had been suffering from headache during the past year, reported headache characteristics, and time of onset. Time‐dependent exposures were used to investigate the impact of SARS‐CoV‐2 infection and vaccination on the risk of new‐onset headache. Headache subtypes were secondary outcomes. Results SARS‐CoV‐2 infection and first and second vaccine doses were associated with increased risk of new‐onset headache. The three cohorts, representing different age groups, were analyzed separately. For pre‐Omicron infections, the hazard ratio (HR) was 6.7 (95% confidence interval (CI) 4.8–9.2) and 6.5 (95% CI 3.8–11.1) among middle‐aged women and men, respectively. For Omicron infection, HRs were 4.7 (95% CI 4.1–5.4) and 4.5 (95% CI 3.7–5.4), respectively. The risk increased with infection severity. Corresponding HRs for first and second vaccine doses, administered during low transmission, were 1.6 and 1.7, respectively, in women, and 1.5 for both doses in men. The third dose, given before the Omicron surge, was associated with 20%–40% protection against new‐onset headache. Conclusions SARS‐CoV‐2 infection was strongly associated with new‐onset headache. Primary vaccination was associated with a small increased risk of headache during a low‐transmission period, whereas booster vaccination offered protection during high‐transmission.

• Brandlistuen, Ragnhild Eek; Kristjansson, Dana; Alsaker, Elin Hilde Roti; Valen, Ragnhild; Birkeland, Even & Røyrvik, Ellen Christine [Show all 15 contributors for this article] (2025). Cohort Profile Update: The Norwegian Mother, Father and Child Cohort (MoBa). International Journal of Epidemiology. ISSN 0300-5771. 54(5). doi: 10.1093/ije/dyaf139. Full text in Research Archive
• Walker, Karen Christina; Specht, Ina O.; Hjortdal, Vibeke; Christesen, Henrik T.; Heitmann, Berit L. & Santorelli, Gillian [Show all 14 contributors for this article] (2025). Circulating 25-Hydroxyvitamin D Levels During Pregnancy and Risk of Congenital Heart Diseases: Multivariable and Mendelian Randomization Analyses Using 3 Birth Cohorts. Journal of the American Heart Association (JAHA). 14(9). doi: 10.1161/JAHA.124.036273. Full text in Research Archive Show summary

  Background: Identifying modifiable risk factors for congenital heart disease (CHD) is important for prevention. Previous studies have reported associations between 25‐hydroxyvitamin D (25(OH)D) in pregnancy and CHD in the offspring. However, these studies contain important methodological limitations. We aimed to investigate 25(OH)D levels during pregnancy in relation to offspring risk of CHD using both multivariable regression (MVR) analysis and Mendelian randomization (MR) analysis. Methods: Data from the ALSPAC (Avon Longitudinal Study of Parents and Children), BiB (Born in Bradford), and MoBa (Norwegian Mother, Father and Child Cohort) studies (N=8722 (77 cases) for MVR analysis, N=74 953 (646 cases) for MR) were used. MVR analysis was adjusted for offspring sex, maternal age, education, body mass index, smoking, alcohol consumption, and parity. One sample MR was performed with weighted genetic risk score for 25(OH)D based on published genome‐wide significant genetic variants. Sensitivity analyses explored the relevance and validity of the genetic risk score. Results were pooled across the 3 cohorts in a meta‐analysis with random effects and consistency between results from the MVR and MR was examined. Results: Pooled results from the adjusted MVR suggested higher maternal pregnancy 25(OH)D associated with lower CHD risk, though the CIs were wide and included the null (odds ratio [OR], 0.79 [95% CI, 0.53, 1.06] per 1 SD higher 25(OH)D). By contrast precise MR results did not support a causal relationship (OR, 0.99 [95% CI, 0.91, 1.07] per 1 SD higher 25(OH)D genetic risk score). Conclusions: We did not find robust evidence supporting an effect of maternal pregnancy 25(OH)D levels on offspring CHD.

• Shaaban, Ahmed Nabil; Andersson, Filip; Thiesmeier, Robert; Orsini, Nicola; Peña, Sebastian & Caspersen, Ida Henriette [Show all 12 contributors for this article] (2025). The association between tobacco use and COVID-19 diagnoses in three Nordic countries: a pooled analysis. European Journal of Public Health. ISSN 1101-1262. 35(1), p. 101–107. doi: 10.1093/eurpub/ckae156. Full text in Research Archive
• Lammi, Vilma; Nakanishi, Tomoko; Jones, Samuel E.; Andrews, Shea J.; Karjalainen, Juha & Cortés, Beatriz [Show all 280 contributors for this article] (2025). Genome-wide association study of long COVID. Nature Genetics. ISSN 1061-4036. 57, p. 1402–1417. doi: 10.1038/s41588-025-02100-w. Full text in Research Archive
• Caspersen, Ida Henriette; Skodvin, Siri Nærland; Blix, Kristine; Robertson, Anna Hayman; Laake, Ida & Feiring, Berit [Show all 9 contributors for this article] (2025). Post-COVID symptoms after SARS-CoV-2 omicron infection and the effect of booster vaccination: A population-based cohort study. Vaccine. ISSN 0264-410X. 47. doi: 10.1016/j.vaccine.2024.126664. Full text in Research Archive
• Lee, Yunsung; Gjerdevik, Miriam; Jugessur, Astanand; Gjessing, Håkon K.; Corfield, Elizabeth Claire & Havdahl, Alexandra [Show all 10 contributors for this article] (2025). Parent-of-Origin Effects in Childhood Asthma at Seven Years of Age. Genetic Epidemiology. ISSN 0741-0395. 49(3). doi: 10.1002/gepi.70007. Full text in Research Archive
• Assary, Elham; Coleman, Jonathan R. I.; Hemani, Gibran; Weijer, Margot P. van de; Howe, Laurence J. & Palviainen, Teemu [Show all 81 contributors for this article] (2025). Genetics of monozygotic twins reveals the impact of environmental sensitivity on psychiatric and neurodevelopmental phenotypes. Nature Human Behaviour. 9, p. 1683–1696. doi: 10.1038/s41562-025-02193-7. Full text in Research Archive Show summary

  Individual sensitivity to environmental exposures may be genetically influenced. This genotype-by-environment interplay implies differences in phenotypic variance across genotypes, but these variants have proven challenging to detect. Genome-wide association studies of monozygotic twin differences are conducted through family-based variance analyses, which are more robust to the systemic biases that impact population-based methods. We combined data from 21,792 monozygotic twins (10,896 pairs) from 11 studies to conduct one of the largest genome-wide association study meta-analyses of monozygotic phenotypic differences, in children, adolescents and adults separately, for seven psychiatric and neurodevelopmental phenotypes: attention deficit hyperactivity disorder symptoms, autistic traits, anxiety and depression symptoms, psychotic-like experiences, neuroticism and wellbeing. The proportions of phenotypic variance explained by single-nucleotide polymorphisms in these phenotypes were estimated (h2 = 0–18%), but were imprecise. We identified 13 genome-wide significant associations (single-nucleotide polymorphisms, genes and gene sets), including genes related to stress reactivity for depression, growth factor-related genes for autistic traits and catecholamine uptake-related genes for psychotic-like experiences. This is the largest genetic study of monozygotic twins to date by an order of magnitude, evidencing an alternative method to study the genetic architecture of environmental sensitivity. The statistical power was limited for some analyses, calling for better-powered future studies.

• Marques, Irene F.; Domènech-Panicello, Carola; Geurtsen, Madelon L.; Hoang, Thanh T.; Richmond, Rebecca & Polinski, Kristen [Show all 24 contributors for this article] (2025). Associations of maternal night shift work during pregnancy with DNA methylation in offspring: a meta-analysis in the PACE consortium. Clinical Epigenetics. 17(1). doi: 10.1186/s13148-024-01810-y. Full text in Research Archive
• Austerberry, Chloe; Zayats, Tetyana; Ronald, Angelica; Corfield, Elizabeth Claire; Smajlagic, Dinka & Havdahl, Alexandra [Show all 11 contributors for this article] (2025). Evocative effects of children's education-associated genetics on maternal parenting: results from the Norwegian mother, father and child cohort study. Journal of Child Psychology and Psychiatry. ISSN 0021-9630. 67(2), p. 158–170. doi: 10.1111/jcpp.70025. Full text in Research Archive Show summary

  Background: It has long been hypothesized that increasing heritability with age of cognitive and educational performance is partly attributable to evocative gene–environment correlation. However, this hypothesis has not been widely tested. Methods: We addressed this gap by examining whether children's education polygenic scores (PGSedu) were associated with maternal self-reported positive and literacy-focused parenting when children were 5 years old, and if evoked parenting differences mediated genetic effects on children's educational outcomes (mother-reported at 6–8 years of age), while controlling for parental PGSedu. We also investigated whether maternal reports of children's language at 5 years old were associated with parenting and mediated genetic effects on educational performance. These questions were addressed in a sample of 83,627 parent-offspring trios from the Norwegian Mother, Father and Child Cohort Study, a longitudinal population-based pregnancy cohort. Results: Children's PGSedu were significantly associated with maternal literacy-focused (β = .03, 95% CI [0.01, 0.05], p = .021) but not positive parenting (β = 0.01, 95% CI [−0.02, 0.05], p = .410), and literacy-focused parenting significantly mediated the effects of children's PGSedu on their educational performance (β = 0.01, 95% CI [1 × 10−3, 0.01], p = .023). Children's language was associated with maternal parenting and mediated the effects of children's PGSedu on their educational performance (β = 0.01, 95% CI [3 × 10−3, 0.02], p = .002). Conclusions: These findings support our hypotheses and suggest early language and parenting may be mechanisms implicated in the pathways from children's genetics to their educational outcomes.

• Walle, Kjersti Mæhlum; Gustavson, Kristin; Mjaaland, Siri; Askeland, Ragna Bugge; Magnus, Per Minor & Susser, Ezra [Show all 12 contributors for this article] (2025). Maternal immune-mediated conditions and ADHD risk in offspring. BMC Medicine. 23, p. 1–15. doi: 10.1186/s12916-025-04227-3. Full text in Research Archive Show summary

  Background Maternal immune-mediated conditions during pregnancy have been linked with increased risk of attention-deficit/hyperactivity disorder (ADHD) in offspring. The relative contributions of maternal inflammatory/immune responses versus shared genetic predispositions remain unclear. This study uses paternal immune-mediated conditions as a negative control to explore these factors, as we investigate associations between maternal immune-mediated conditions during pregnancy and offspring ADHD. Methods Prospective data from the Norwegian Mother, Father, and Child Cohort Study (MoBa) was linked with the Medical Birth Registry of Norway (MBRN) and the Norwegian Patient Registry (NPR) to assess associations between prenatal exposure to maternal immune-mediated conditions and offspring ADHD risk up to age 18. Nationwide recruitment from 1999 to 2008 yielded 104,270 eligible mother–child pairs, with 21,340 children exposed to maternal allergic conditions (asthma, allergies, atopic conditions) and 7478 to other immune conditions (autoimmune, inflammatory). Paternal self-reported immune conditions served as negative controls. Children’s ADHD diagnoses were obtained from NPR, and Cox proportional hazard models estimated hazard ratios for ADHD. Results Both overall categories were associated with increased offspring ADHD risk (allergic conditions HR 1.23, 95% CI, 1.14–1.34; other immune conditions HR 1.36, 95% CI, 1.21–1.53). Specific associations included maternal asthma (HR 1.47, 95% CI, 1.30–1.67), allergies (HR 1.20, 95% CI, 1.10–1.31), rheumatologic/musculoskeletal conditions (HR 1.64, 95% CI, 1.28–2.10), Crohn’s disease/ulcerative colitis (adjusted HR 1.95, 95% CI, 1.23–3.09), and endocrine conditions (HR 1.42, 95% CI, 1.15–1.77), specifically, type 1 diabetes (adjusted HR 2.50, 95% CI, 1.66–3.75). Although some paternal immune-mediated conditions (psoriasis, ulcerative colitis, Crohn’s disease) showed similar trends in ADHD risk, only paternal asthma was significantly associated (adjusted HR 1.26, 95% CI, 1.10–1.45). Conclusions Several maternal immune-mediated conditions were associated with increased offspring ADHD risk. The higher, more consistent ADHD risk estimates with maternal conditions compared to paternal ones indicate that unmeasured genetic confounding does not fully explain these associations. These results suggest direct effects on fetal development through events at the maternal–fetal interface which may alter fetal immune responses and lead to greater ADHD risk in offspring. Asthma may be an exception to this mechanism, as paternal asthma was also linked with offspring ADHD risk.

• Kweon, Hyeokmoon; Burik, Casper A. P.; Ning, Yuchen; Ahlskog, Rafael; Xia, Charley & Abner, Erik [Show all 68 contributors for this article] (2025). Associations between common genetic variants and income provide insights about the socio-economic health gradient. Nature Human Behaviour. 9, p. 794–805. doi: 10.1038/s41562-024-02080-7. Full text in Research Archive Show summary

  We conducted a genome-wide association study on income among individuals of European descent (N = 668,288) to investigate the relationship between socio-economic status and health disparities. We identified 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes (the Income Factor). Our polygenic index captures 1–5% of income variance, with only one fourth due to direct genetic effects. A phenome-wide association study using this index showed reduced risks for diseases including hypertension, obesity, type 2 diabetes, depression, asthma and back pain. The Income Factor had a substantial genetic correlation (0.92, s.e. = 0.006) with educational attainment. Accounting for the genetic overlap of educational attainment with income revealed that the remaining genetic signal was linked to better mental health but reduced physical health and increased risky behaviours such as drinking and smoking. These findings highlight the complex genetic influences on income and health.

• Peña, Sebastián; Zhou, Zhi; Kestilä, Laura; Galanti, Maria Rosaria; Shaaban, Ahmed Nabil & Caspersen, Ida Henriette [Show all 12 contributors for this article] (2024). Tobacco Use and Uptake of COVID-19 Vaccinations in Finland: A Population-Based Study. Nicotine & Tobacco Research. ISSN 1462-2203. 26(11), p. 1553–1562. doi: 10.1093/ntr/ntad234. Full text in Research Archive
• Mukherjee, Ratnadeep; Eggesbø, Linn Margrethe; Wolf, Asia-Sophia Fumika Michaela; Kjønstad, Ingrid Fadum; Solum, Guri & Ravussin, Anthony [Show all 13 contributors for this article] (2024). Mass cytometry reveals cellular correlates of immune response heterogeneity to SARS-CoV-2 vaccination in the elderly. npj Vaccines. 9(1). doi: 10.1038/s41541-024-01028-2. Full text in Research Archive
• Borges, Maria Carolina; Clayton, Gemma L.; Freathy, Rachel M.; Felix, Janine F.; Fernández-Sanlés, Alba & Soares, Ana Gonçalves [Show all 40 contributors for this article] (2024). Integrating multiple lines of evidence to assess the effects of maternal BMI on pregnancy and perinatal outcomes. BMC Medicine. 22. doi: 10.1186/s12916-023-03167-0. Full text in Research Archive
• Bohlin, Jon; Håberg, Siri Eldevik; Magnus, Per Minor & Gjessing, Håkon K. (2024). MinLinMo: a minimalist approach to variable selection and linear model prediction. BMC Bioinformatics. 25. doi: 10.1186/s12859-024-06000-4. Full text in Research Archive Show summary

  Generating prediction models from high dimensional data often result in large models with many predictors. Causal inference for such models can therefore be difficult or even impossible in practice. The stand-alone software package MinLinMo emphasizes small linear prediction models over highest possible predictability with a particular focus on including variables correlated with the outcome, minimal memory usage and speed. MinLinMo is demonstrated on large epigenetic datasets with prediction models for chronological age, gestational age, and birth weight comprising, respectively, 15, 14 and 10 predictors. The parsimonious MinLinMo models perform comparably to established prediction models requiring hundreds of predictors.

• Belanger, Sissel Marguerite; Hauge, Lars Johan; Reneflot, Anne; Øien-Ødegaard, Carine; Christiansen, Solveig Tobie Glestad & Magnus, Per Minor [Show all 7 contributors for this article] (2024). General practitioner consultations for mental health reasons prior to and following bereavement by suicide. Social Psychiatry and Psychiatric Epidemiology. ISSN 0933-7954. 59, p. 1533–1541. doi: 10.1007/s00127-023-02607-9. Full text in Research Archive
• Verhoef, Ellen; Allegrini, Andrea G.; Jansen, Philip R.; Lange, Katherine; Wang, Carol A. & Morgan, Angela T. [Show all 64 contributors for this article] (2024). Genome-Wide Analyses of Vocabulary Size in Infancy and Toddlerhood: Associations With Attention-Deficit/Hyperactivity Disorder, Literacy, and Cognition-Related Traits. Biological Psychiatry. ISSN 0006-3223. 95(9), p. 859–869. doi: 10.1016/j.biopsych.2023.11.025. Full text in Research Archive
• Nyquist, Cecilie Bjertness; Torgersen, Leila; David, Linda W.; Diseth, Trond Haaken; Magnus, Per Minor & Biele, Guido [Show all 7 contributors for this article] (2024). Population-adjusted numbers, demographics and mental health among children and adolescents referred to the Norwegian National Center for Gender Incongruence over two decades. European Child and Adolescent Psychiatry. ISSN 1018-8827. doi: 10.1007/s00787-024-02508-5. Full text in Research Archive Show summary

  Over the last decade, there has been a sharp increase in young people seeking medical treatment for gender dysphoria/gender incongruence (GD/GI). The aims of this study were to calculate yearly population-adjusted numbers of children and adolescents referred to the Norwegian National Center for Gender Incongruence (NCGI) at Oslo University Hospital (OUS) from 2000 to 2022; to describe the demographic characteristics and prevalence of psychiatric diagnoses, self-harm and suicide attempts among the referred from 2000 to 2020; and to investigate time trends. The study used data from the Gender Incongruence Registry for Children and Adolescents (GIRCA) in Norway. All persons under 18 years (n = 1258) referred to the NCGI between 2000 and 2020 were included: 68.4% assigned female gender at birth (AFAB) and 31.6% assigned male gender at birth (AMAB). We found a sharp increase in referrals to the NCGI favouring AFAB over AMAB. Nearly two in three (64.5%) had one or more registered psychiatric diagnoses. Self-harm was registered among 35.5%, and 12.7% had attempted suicide. Registered psychiatric diagnoses were significantly (p ≤ 0.001) more prevalent among AFAB (67.8%) than AMAB (57.4%). The number of registered diagnoses per person decreased significantly over time, with an average reduction of 0.02 diagnoses per person per year. Although there was a downward time trend in registered diagnoses per person, the total mental health burden among children and adolescents with GI emphasizes the need for a holistic approach.

• Skåra, Karoline Hansen; Lee, Yunsung; Jugessur, Astanand; Gjessing, Håkon K.; AVIV, Abraham & Brumpton, Ben Michael [Show all 11 contributors for this article] (2024). Telomere length in relation to fecundability and use of assisted reproductive technologies: the Norwegian Mother, Father, and Child Cohort Study. Research Square. ISSN 2693-5015. doi: 10.21203/rs.3.rs-4430021/v1. Full text in Research Archive
• Yang, Qian; Magnus, Maria Christine; Kilpi, Fanny; Santorelli, Gillian; Soares, Ana Goncalves & West, Jane [Show all 12 contributors for this article] (2024). Evaluating causal associations of chronotype with pregnancy and perinatal outcomes and its interactions with insomnia and sleep duration: a mendelian randomization study. BMC Pregnancy and Childbirth. 24(1), p. 1–11. doi: 10.1186/s12884-024-07023-8. Full text in Research Archive
• Askelund, Adrian Dahl; Wootton, Robyn E.; Torvik, Fartein A.; Lawn, Rebecca B.; Ask, Helga & Corfield, Elizabeth C. [Show all 15 contributors for this article] (2024). Assessing causal links between age at menarche and adolescent mental health: a Mendelian randomisation study. BMC Medicine. 22(1). doi: 10.1186/s12916-024-03361-8. Full text in Research Archive Show summary

  Background: The timing of puberty may have an important impact on adolescent mental health. In particular, earlier age at menarche has been associated with elevated rates of depression in adolescents. Previous research suggests that this relationship may be causal, but replication and an investigation of whether this effect extends to other mental health domains is warranted. Methods: In this Registered Report, we triangulated evidence from different causal inference methods using a new wave of data (N = 13,398) from the Norwegian Mother, Father, and Child Cohort Study. We combined multiple regression, one- and two-sample Mendelian randomisation (MR), and negative control analyses (using pre-pubertal symptoms as outcomes) to assess the causal links between age at menarche and different domains of adolescent mental health. Results: Our results supported the hypothesis that earlier age at menarche is associated with elevated depressive symptoms in early adolescence based on multiple regression (β =  − 0.11, 95% CI [− 0.12, − 0.09], pone-tailed < 0.01). One-sample MR analyses suggested that this relationship may be causal (β =  − 0.07, 95% CI [− 0.13, 0.00], pone-tailed = 0.03), but the effect was small, corresponding to just a 0.06 standard deviation increase in depressive symptoms with each earlier year of menarche. There was also some evidence of a causal relationship with depression diagnoses during adolescence based on one-sample MR (OR = 0.74, 95% CI [0.54, 1.01], pone-tailed = 0.03), corresponding to a 29% increase in the odds of receiving a depression diagnosis with each earlier year of menarche. Negative control and two-sample MR sensitivity analyses were broadly consistent with this pattern of results. Multivariable MR analyses accounting for the genetic overlap between age at menarche and childhood body size provided some evidence of confounding. Meanwhile, we found little consistent evidence of effects on other domains of mental health after accounting for co-occurring depression and other confounding. Conclusions: We found evidence that age at menarche affected diagnoses of adolescent depression, but not other domains of mental health. Our findings suggest that earlier age at menarche is linked to problems in specific domains rather than adolescent mental health in general.

• Magnus, Maria Christine; Lee, Yunsung; Carlsen, Ellen Øen; Arge, Lise Andrea; Jugessur, Astanand & Kvalvik, Liv Grimstvedt [Show all 11 contributors for this article] (2024). Parental epigenetic age acceleration and risk of adverse birth outcomes: the Norwegian mother, father and child cohort study. BMC Medicine. 22(1). doi: 10.1186/s12916-024-03780-7. Full text in Research Archive Show summary

  Background Few studies have examined associations between maternal epigenetic age acceleration and adverse birth outcomes, and none have investigated paternal epigenetic age acceleration. Our objective was to assess the associations of parental (both maternal and paternal) epigenetic age acceleration in relation to birth outcomes. Methods Parental epigenetic age was estimated using seven established epigenetic clocks in 2198 mothers and 2193 fathers from the Norwegian Mother, Father, and Child Cohort Study (MoBa). Individual epigenetic age acceleration was then calculated as residuals from linear regressions of estimates from the epigenetic clocks on chronological age. Further, linear regression was used to analyze differences in continuous outcomes (gestational length and standardized birthweight), while logistic regression was used for binary outcomes (preterm birth, post-term birth, small-for-gestational age [SGA], large-for-gestational age [LGA], and pre-eclampsia), adjusting for chronological age, parity, educational level, smoking, and BMI. Results Increasing maternal, but not paternal, epigenetic age acceleration was associated with decreased gestational length for five out of six clocks, with adjusted estimates ranging from a mean 0.51-day decrease (95% CI − 1.00, − 0.02; p-value 0.043) for the Horvath clock to a 0.80-day decrease (95% CI − 1.29, − 0.31; p-value 0.002) for the Levine clock. An association with increasing maternal epigenetic age acceleration according to the DunedinPACE clock was also seen with greater standardized birthweight [mean difference 0.08 (95% CI 0.04, 0.12; p-value < 0.001]. These results were also reflected in an increased risk of spontaneous preterm birth and LGA. No associations were observed with post-term birth, SGA, or pre-eclampsia. Conclusions Maternal, but not paternal, epigenetic age acceleration is associated with shorter pregnancies and an increased risk of spontaneous preterm birth. This may suggest that women’s biological age acceleration, including factors such as metabolic and physiologic state, is an additional risk factor for preterm delivery, beyond chronological age.

• Solé-Navais, Pol; Juodakis, Julius; Ytterberg, Karin; Wu, Xiaoping; Bradfield, Jonathan P. & Vaudel, Marc [Show all 23 contributors for this article] (2024). Genome-wide analyses of neonatal jaundice reveal a marked departure from adult bilirubin metabolism. Nature Communications. 15(1). doi: 10.1038/s41467-024-51947-w. Full text in Research Archive Show summary

  Jaundice affects almost all neonates in their first days of life and is caused by the accumulation of bilirubin. Although the core biochemistry of bilirubin metabolism is well understood, it is not clear why some neonates experience more severe jaundice and require treatment with phototherapy. Here, we present the first genome-wide association study of neonatal jaundice to date in nearly 30,000 parent-offspring trios from Norway (cases ≈ 2000). The alternate allele of a common missense variant affecting the sequence of UGT1A4 reduces the susceptibility to jaundice five-fold, which replicated in separate cohorts of neonates of African American and European ancestries. eQTL colocalization analyses indicate that the association may be driven by regulation of UGT1A1 in the intestines, but not in the liver. Our results reveal marked differences in the genetic variants involved in neonatal jaundice compared to those regulating bilirubin levels in adults, suggesting distinct genetic mechanisms for the same biological pathways.

• Magnus, Maria Christine; Caspersen, Ida Henriette; Wensaas, Knut-Arne; Eide, Helena Niemi; Örtqvist, Anne K. & Oakley, Laura L. [Show all 8 contributors for this article] (2024). Covid-19 vaccination and menstrual bleeding disturbances among women of fertile age: a Norwegian registry study. European Journal of Epidemiology (EJE). ISSN 0393-2990. 39, p. 1127–2238. doi: 10.1007/s10654-024-01170-0. Full text in Research Archive
• Camba, Alvaro Hernaez; Skåra, Karoline Hansen; Page, Christian Magnus; Mitter, Vera R.; Hernández, Marta H. & Magnus, Per Minor [Show all 16 contributors for this article] (2024). Parental genetically predicted liability for coronary heart disease and risk of adverse pregnancy outcomes: a cohort study. BMC Medicine. 22. doi: 10.1186/s12916-023-03223-9. Full text in Research Archive Show summary

  Background Adverse pregnancy outcomes (APO) may unmask or exacerbate a woman’s underlying risk for coronary heart disease (CHD). We estimated associations of maternal and paternal genetically predicted liability for CHD with lifelong risk of APOs. We hypothesized that associations would be found for women, but not their male partners (negative controls). Methods We studied up to 83,969‬ women (and up to 55,568‬ male partners) from the Norwegian Mother, Father and Child Cohort Study or the Trøndelag Health Study with genotyping data and lifetime history of any APO in their pregnancies (1967–2019) in the Medical Birth Registry of Norway (miscarriage, stillbirth, hypertensive disorders of pregnancy, gestational diabetes, small for gestational age, large for gestational age, and spontaneous preterm birth). Maternal and paternal genetic risk scores (GRS) for CHD were generated using 148 gene variants (p-value < 5 × 10−8, not in linkage disequilibrium). Associations between GRS for CHD and each APO were determined using logistic regression, adjusting for genomic principal components, in each cohort separately, and combined using fixed effects meta-analysis. Results One standard deviation higher GRS for CHD in women was related to increased risk of any hypertensive disorders of pregnancy (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.05–1.10), pre-eclampsia (OR 1.08, 95% CI 1.05–1.11), and small for gestational age (OR 1.04, 95% CI 1.01–1.06). Imprecise associations with lower odds of large for gestational age (OR 0.98, 95% CI 0.96–1.00) and higher odds of stillbirth (OR 1.04, 95% CI 0.98–1.11) were suggested. These findings remained consistent after adjusting for number of total pregnancies and the male partners’ GRS and restricting analyses to stable couples. Associations for other APOs were close to the null. There was weak evidence of an association of paternal genetically predicted liability for CHD with spontaneous preterm birth in female partners (OR 1.02, 95% CI 0.99–1.05), but not with other APOs. Conclusions Hypertensive disorders of pregnancy, small for gestational age, and stillbirth may unmask women with a genetically predicted propensity for CHD. The association of paternal genetically predicted CHD risk with spontaneous preterm birth in female partners needs further exploration.

• Moksnes, Marta R.; Hansen, Ailin F.; Wolford, Brooke N.; Thomas, Laurent F.; Rasheed, Humaira & Simic, Anica [Show all 24 contributors for this article] (2024). A genome-wide association study provides insights into the genetic etiology of 57 essential and non-essential trace elements in humans. Communications Biology. 7(1). doi: 10.1038/s42003-024-06101-z. Full text in Research Archive Show summary

  Trace elements are important for human health but may exert toxic or adverse effects. Mechanisms of uptake, distribution, metabolism, and excretion are partly under genetic control but have not yet been extensively mapped. Here we report a comprehensive multi-element genome-wide association study of 57 essential and non-essential trace elements. We perform genome-wide association meta-analyses of 14 trace elements in up to 6564 Scandinavian whole blood samples, and genome-wide association studies of 43 trace elements in up to 2819 samples measured only in the Trøndelag Health Study (HUNT). We identify 11 novel genetic loci associated with blood concentrations of arsenic, cadmium, manganese, selenium, and zinc in genome-wide association meta-analyses. In HUNT, several genome-wide significant loci are also indicated for other trace elements. Using two-sample Mendelian randomization, we find several indications of weak to moderate effects on health outcomes, the most precise being a weak harmful effect of increased zinc on prostate cancer. However, independent validation is needed. Our current understanding of trace element-associated genetic variants may help establish consequences of trace elements on human health.

• Hernandez, Marta H.; Cohen, Jacqueline Mallory; Skåra, Karoline Hansen; Grindstad, Thea Karoline Walstad; Lee, Yunsung & Magnus, Per [Show all 14 contributors for this article] (2024). Placental efflux transporters and antiseizure or antidepressant medication use impact birth weight in MoBa cohort. iScience. 27(3). doi: 10.1016/j.isci.2024.109285. Full text in Research Archive Show summary

  Low birth weight raises neonatal risks and lifelong health issues and is linked to maternal medication use during pregnancy. We examined data from the Norwegian Mother, Father, and Child Cohort Study and the Medical Birth Registry of Norway, including 69,828 offspring with genotype data and 81,189 with maternal genotype data. We identified genetic risk variants in placental efflux transporters, calculated genetic scores based on alleles related to transporter activity, and assessed their interaction with prenatal use of antiseizure or antidepressant medication on offspring birth weight. Our study uncovered possible genetic variants in both offspring (rs3740066) and mothers (rs10248420; rs2235015) in placental efflux transporters (MRP2-ABCC2 and MDR1-ABCB1) that modulated the association between prenatal exposure to antiseizure medication and low birth weight in the offspring. Antidepressant exposure was associated with low birth weight, but there were no gene-drug interactions. The interplay between MRP2-ABCC2 and MDR1-ABCB1 variants and antiseizure medication may impact neonatal birth weight.

• Skåra, Karoline Hansen; Lee, Yunsung; Jugessur, Astanand; Gjessing, Håkon K.; Aviv, Abraham & Brumpton, Ben Michael [Show all 11 contributors for this article] (2024). Telomere length in relation to fecundability and use of assisted reproductive technologies: the Norwegian Mother, Father, and Child Cohort Study. BMC Medicine. 22(1). doi: 10.1186/s12916-024-03795-0. Full text in Research Archive Show summary

  Background: Telomere length (TL) has been reported to be associated with conditions such as endometriosis and polycystic ovary syndrome, with some studies finding associations with shorter TL and others with longer TL. In men, studies mostly report associations between shorter TL and sperm quality. To our knowledge, no studies have thus far investigated associations between TL and fecundability or the use of assisted reproductive technologies (ART). Methods: This study is based on the Norwegian Mother, Father, and Child Cohort (MoBa) Study and uses data from the Medical Birth Registry of Norway (MBRN). We included women (24,645 with genotype data and 1054 with TL measurements) and men (18,339 with genotype data and 965 with TL measurements) participating between 1998 and 2008. We investigated associations between leukocyte TL (LTL) and fecundability (defined as the probability to conceive within a given menstrual cycle), infertility (defined has having spent 12 months or more trying to conceive without success), and ART use. We also repeated the analyses using instrumental variables for LTL consisting of genetic risk scores for LTL and genetically predicted LTL. Results: Approximately 11% of couples had experienced infertility and 4% had used ART. LTL was not associated with fecundability in women (fecundability ratio [FR], 0.98; 95% confidence interval [CI], 0.92–1.04) or men (FR, 0.99; CI, 0.93–1.06), nor with infertility in women (odds ratio [OR], 1.03; CI, 0.85–1.24) or men (OR, 1.05; CI, 0.87–1.28). We observed an increased likelihood of using ART with increasing LTL in men (OR, 1.22; CI, 1.03–1.46), but not in women (OR, 1.10; CI, 0.92–1.31). No significant associations were observed using the instrumental variables for LTL. Conclusions: We found no indication that LTL is a suitable biomarker for assessing fecundability, infertility, or ART use. Additional studies are required to replicate the association observed between LTL and ART use in men.

• Westergaard, David; Steinthorsdottir, Valgerdur; Stefansdottir, Lilja; Rohde, Palle Duun; Wu, Xiaoping & Geller, Frank [Show all 41 contributors for this article] (2024). Genome-wide association meta-analysis identifies five loci associated with postpartum hemorrhage. Nature Genetics. ISSN 1061-4036. 56, p. 1597–1603. doi: 10.1038/s41588-024-01839-y. Full text in Research Archive Show summary

  Bleeding in early pregnancy and postpartum hemorrhage (PPH) bear substantial risks, with the former closely associated with pregnancy loss and the latter being the foremost cause of maternal death, underscoring the severe impact on maternal–fetal health. We identified five genetic loci linked to PPH in a meta-analysis. Functional annotation analysis indicated candidate genes HAND2, TBX3 and RAP2C/FRMD7 at three loci and showed that at each locus, associated variants were located within binding sites for progesterone receptors. There were strong genetic correlations with birth weight, gestational duration and uterine fibroids. Bleeding in early pregnancy yielded no genome-wide association signals but showed strong genetic correlation with various human traits, suggesting a potentially complex, polygenic etiology. Our results suggest that PPH is related to progesterone signaling dysregulation, whereas early bleeding is a complex trait associated with underlying health and possibly socioeconomic status and may include genetic factors that have not yet been identified.

• Ollila, Hanna M.; Fonseca-Rodríguez, Osvaldo; Caspersen, Ida Henriette; Kalucza, Sebastian; Normark, Johan & Trogstad, Lill [Show all 11 contributors for this article] (2024). How do clinicians use post-COVID syndrome diagnosis? Analysis of clinical features in a Swedish COVID-19 cohort with 18 months’ follow-up: a national observational cohort and matched cohort study. BMJ Public Health. 2, p. 1–10. doi: 10.1136/bmjph-2023-000336. Full text in Research Archive
• Tunheim, Gro; Fossum, Even; Robertson, Anna Hayman; Rø, Gunnar Øyvind Isaksson; Chopra, Adity & Vaage, John T. [Show all 13 contributors for this article] (2024). Characterization of the SARS-CoV-2 antibody landscape in Norway in the late summer of 2022: high seroprevalence in all age groups with patterns of primary Omicron infection in children and hybrid immunity in adults. BMC Infectious Diseases. 24:841(1), p. 1–20. doi: 10.1186/s12879-024-09670-w. Full text in Research Archive Show summary

  Background According to Norwegian registries, 91% of individuals ≥ 16 years had received ≥ 1 dose of COVID-19 vaccine by mid-July 2022, whereas less than 2% of children < 12 years were vaccinated. Confirmed COVID-19 was reported for 27% of the population, but relaxation of testing lead to substantial underreporting. We have characterized the humoral immunity to SARS-CoV-2 in Norway in the late summer of 2022 by estimating the seroprevalence and identifying antibody profiles based on reactivity to Wuhan or Omicron-like viruses in a nationwide cross-sectional collection of residual sera, and validated our findings using cohort sera. Methods 1,914 anonymized convenience sera and 243 NorFlu-cohort sera previously collected from the Oslo-area with reported infection and vaccination status were analyzed for antibodies against spike, the receptor-binding domain (RBD) of the ancestral Wuhan strain and Omicron BA.2 RBD, and nucleocapsid (N). Samples were also tested for antibodies inhibiting RBD-ACE2 interaction. Neutralization assays were performed on subsets of residual sera against B.1, BA.2, XBB.1.5 and BQ.1.1. Results The national seroprevalence estimate from vaccination and/or infection was 99.1% (95% CrI 97.0-100.0%) based on Wuhan (spike_W and RBD_W) and RBD_BA2 antibodies. Sera from children < 12 years had 2.2 times higher levels of antibodies against RBD_BA2 than RBD_W and their seroprevalence estimate showed a 14.4 percentage points increase when also including anti-RBD_BA2 antibodies compared to Wuhan-antibodies alone. 50.3% (95% CI 45.0-55.5%) of residual sera from children and 38.1% (95% CI 36.0-40.4%) of all residual sera were positive for anti-N-antibodies. By combining measurements of binding- and ACE2-RBD-interaction-inhibiting antibodies, reactivity profiles indicative of infection and vaccination history were identified and validated using cohort sera. Residual sera with a profile indicative of hybrid immunity were able to neutralize newer Omicron variants XBB.1.5 and BQ.1.1. Conclusions By late summer of 2022, most of the Norwegian population had antibodies to SARS-CoV-2, and almost all children had been infected. Antibody profiles indicated that children mostly had experienced a primary Omicron infection, while hybrid immunity was common among adults. The finding that sera displaying hybrid immunity could neutralize newer Omicron variants indicates that Wuhan-like priming of the immune response did not have a harmful imprinting effect and that infections induce cross-reacting antibodies against future variants.

• Lee, Yunsung; Jugessur, Astanand; Gjessing, Håkon K.; Harris, Jennifer Ruth; Susser, Ezra & Magnus, Per Minor [Show all 7 contributors for this article] (2024). Effect of polygenic scores of telomere length alleles on telomere length in newborns and parents. Aging Cell. ISSN 1474-9718. 23(9). doi: 10.1111/acel.14241. Full text in Research Archive Show summary

  In adults, polygenic scores (PGSs) of telomere length (TL) alleles explain about 4.5% of the variance in TL, as measured by quantitative polymerase chain reaction (qPCR). Yet, these PGSs strongly infer a causal role of telomeres in aging-related diseases. To better understand the determinants of TL through the lifespan, it is essential to examine to what extent these PGSs explain TL in newborns. This study investigates the effect of PGSs on TL in both newborns and their parents, with TL measured by Southern blotting and expressed in base-pairs (bp). Additionally, the study explores the impact of PGSs related to transmitted or non-transmitted alleles on TL in newborns. For parents and newborns, the PGS effects on TL were 172 bp (p =  2.03 × 10−15) and 161 bp (p =  3.06 × 10−8), explaining 6.6% and 5.2% of the TL variance, respectively. The strongest PGS effect was shown for maternally transmitted alleles in newborn girls, amounting to 214 bp (p =  3.77 × 10−6) and explaining 7.8% of the TL variance. The PGS effect of non-transmitted alleles was 56 bp (p = 0.0593) and explained 0.6% of the TL variance. Our findings highlight the importance of TL genetics in understanding early-life determinants of TL. They point to the potential utility of PGSs composed of TL alleles in identifying susceptibility to aging-related diseases from birth and reveal the presence of sexual dimorphism in the effect of TL alleles on TL in newborns. Finally, we attribute the higher TL variance explained by PGSs in our study to TL measurement by Southern blotting.

• He, Jian-Rong; Tikellis, Gabriella; Paltiel, Ora; Klebanoff, Mark; Magnus, Per Minor & Northstone, Kate [Show all 15 contributors for this article] (2024). Association of common maternal infections with birth outcomes: a multinational cohort study. Infection. ISSN 0300-8126. 52, p. 1553–1561. doi: 10.1007/s15010-024-02291-0. Full text in Research Archive
• Ravussin, Anthony; Robertson, Anna Hayman; Wolf, Asia-Sophia Fumika Michaela; Blix, Kristine; Kjønstad, Ingrid Fadum & Solum, Guri [Show all 13 contributors for this article] (2023). Determinants of humoral and cellular immune responses to three doses of mRNA SARS-CoV-2 vaccines in older adults: a longitudinal cohort study. The Lancet Healthy Longevity. 4(5), p. e188–e199. doi: 10.1016/S2666-7568(23)00055-7. Full text in Research Archive Show summary

  Background Older age is associated with poorer outcomes to COVID-19 infection. The Norwegian Institute of Public Health established a longitudinal cohort of adults aged 65–80 years to study the effects of the COVID-19 pandemic. Here we describe the characteristics of the cohort in general, and specifically the immune responses at baseline and after primary and booster vaccination in a subset of longitudinal blood samples, and the epidemiological factors affecting these responses. Methods 4551 participants were recruited, with humoral (n=299) and cellular (n=90) responses measured before vaccination and after two and three vaccine doses. Information on general health, infections, and vaccinations were obtained from questionnaires and national health registries. Findings Half of the participants had a chronic condition. 849 (18·7%) of 4551 were prefrail and 184 (4%) of 4551 were frail. 483 (10·6%) of 4551 had general activity limitations (scored with the Global Activity Limitation Index). After dose two, 295 (98·7%) of 299 participants were seropositive for anti-receptor binding domain IgG, and 210 (100%) of 210 participants after dose three. Spike-specific CD4 and CD8 T cell responses showed high heterogeneity after vaccination and responded to the alpha (B.1.1.7), delta (B.1.617.2), and omicron (B.1.1.529 or BA.1) variants of concern. Cellular responses to seasonal coronaviruses increased after SARS-CoV-2 vaccination. Heterologous prime boosting with mRNA vaccines was associated with the highest antibody (p=0·019) and CD4 T cell responses (p=0·003), and hypertension with lower antibody levels after three doses (p=0·04). Interpretation Most older adults, including those with comorbidities, generated good serological and cellular responses after two vaccine doses. Responses further improved after three doses, particularly after heterologous boosting. Vaccination also generated cross-reactive T cells against variants of concern and seasonal coronaviruses. Frailty was not associated with impaired immune responses, but hypertension might indicate reduced responsiveness to vaccines even after three doses. Individual differences identified through longitudinal sampling enables better prediction of the variability of vaccine responses, which can help guide future policy on the need for subsequent doses and their timing.

• Galanti, Maria Rosaria; Andersson, Filip; Caspersen, Ida Henriette; Peña, Sebastián; Karvonen, Sakari & Magnus, Per Minor [Show all 12 contributors for this article] (2023). Current tobacco use and COVID-19 diagnoses in a cohort of adult clients of public dental clinics in Sweden. Scientific Reports. 13, p. 1–9. doi: 10.1038/s41598-023-28091-4. Full text in Research Archive
• Che, Xiaoyu; Roy, Ayan; Bresnahan, Michaeline; Mjaaland, Siri; Reichborn-Kjennerud, Ted & Magnus, Per Minor [Show all 12 contributors for this article] (2023). Metabolomic analysis of maternal mid-gestation plasma and cord blood in autism spectrum disorders. Molecular Psychiatry. ISSN 1359-4184. 28, p. 2355–2369. doi: 10.1038/s41380-023-02051-w. Full text in Research Archive
• Trogstad, Lill; Laake, Ida; Robertson, Anna Hayman; Mjaaland, Siri; Caspersen, Ida Henriette & Juvet, Lene Kristine [Show all 9 contributors for this article] (2023). Heavy bleeding and other menstrual disturbances in young women after COVID-19 vaccination. Vaccine. ISSN 0264-410X. 41(36), p. 5271–5282. doi: 10.1016/j.vaccine.2023.06.088. Full text in Research Archive
• Camba, Alvaro Hernaez; Lee, Yunsung; Page, Christian Magnus; Skåra, Karoline Hansen; Håberg, Siri Eldevik & Magnus, Per Minor [Show all 14 contributors for this article] (2023). Impaired glucose tolerance and cardiovascular risk factors in relation to infertility: A Mendelian randomization analysis in the Norwegian Mother, Father, and Child Cohort Study. Human Reproduction. ISSN 0268-1161. 39(2), p. 436–441. doi: 10.1093/humrep/dead234. Full text in Research Archive Show summary

  Study question: Are impaired glucose tolerance (as measured by fasting glucose, glycated hemoglobin, and fasting insulin) and cardiovascular disease risk (as measured by low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and diastolic blood pressure) causally related to infertility? Summary answer: Genetic instruments suggest that higher fasting insulin may increase infertility in women. What is known already: Observational evidence suggests a shared etiology between impaired glucose tolerance, cardiovascular risk, and fertility problems. Study design, size, duration: This study included two-sample Mendelian randomization (MR) analyses, in which we used genome-wide association summary data that were publicly available for the biomarkers of impaired glucose tolerance and cardiovascular disease, and sex-specific genome-wide association studies (GWASs) of infertility conducted in the Norwegian Mother, Father, and Child Cohort Study. Participants/materials, setting, methods: There were 68 882 women (average age 30, involved in 81 682 pregnancies) and 47 474 of their male partners (average age 33, 55 744 pregnancies) who had available genotype data and who provided self-reported information on time-to-pregnancy and use of ARTs. Of couples, 12% were infertile (having tried to conceive for ≥12 months or used ARTs to conceive). We applied the inverse variance weighted method with random effects to pool data across variants and a series of sensitivity analyses to explore genetic instrument validity. (We checked the robustness of genetic instruments and the lack of unbalanced horizontal pleiotropy, and we used methods that are robust to population stratification.) Findings were corrected for multiple comparisons by the Bonferroni method (eight exposures: P-value < 0.00625). Main results and the role of chance: In women, increases in genetically determined fasting insulin levels were associated with greater odds of infertility (+1 log(pmol/l): odds ratio 1.60, 95% CI 1.17 to 2.18, P-value = 0.003). The results were robust in the sensitivity analyses exploring the validity of MR assumptions and the role of pleiotropy of other cardiometabolic risk factors. There was also evidence of higher glucose and glycated hemoglobin causing infertility in women, but the findings were imprecise and did not pass our P-value threshold for multiple testing. The results for lipids and blood pressure were close to the null, suggesting that these did not cause infertility. Limitations, reasons for caution: We did not know if underlying causes of infertility were in the woman, man, or both. Our analyses only involved couples who had conceived. We did not have data on circulating levels of cardiometabolic risk factors, and we opted to conduct an MR analysis using GWAS summary statistics. No sex-specific genetic instruments on cardiometabolic risk factors were available. Our results may be affected by selection and misclassification bias. Finally, the characteristics of our study sample limit the generalizability of our results to populations of non-European ancestry. Wider implications of the findings: Treatments for lower fasting insulin levels may reduce the risk of infertility in women.

• Lovik, Anikó; González-Hijón, Juan; Hoffart, Asle; Fawns-Ritchie, Chloe; Magnúsdóttir, Ingibjörg & Lu, Li [Show all 27 contributors for this article] (2023). Elevated symptoms of depression and anxiety among family members and friends of critically ill COVID-19 patients – an observational study of five cohorts across four countries. The Lancet Regional Health - Europe. 33. doi: 10.1016/j.lanepe.2023.100733. Full text in Research Archive Show summary

  Background Little is known regarding the mental health impact of having a significant person (family member and/or close friend) with COVID-19 of different severity. Methods The study included five prospective cohorts from four countries (Iceland, Norway, Sweden, and the UK) with self-reported data on COVID-19 and symptoms of depression and anxiety during March 2020–March 2022. We calculated prevalence ratios (PR) of depression and anxiety in relation to having a significant person with COVID-19 and performed a longitudinal analysis in the Swedish cohort to describe temporal patterns. Findings 162,237 and 168,783 individuals were included in the analysis of depression and anxiety, respectively, of whom 24,718 and 27,003 reported a significant person with COVID-19. Overall, the PR was 1.07 (95% CI: 1.05–1.10) for depression and 1.08 (95% CI: 1.03–1.13) for anxiety in relation to having a significant person with COVID-19. The respective PRs for depression and anxiety were 1.15 (95% CI: 1.08–1.23) and 1.24 (95% CI: 1.14–1.34) if the patient was hospitalized, 1.42 (95% CI: 1.27–1.57) and 1.45 (95% CI: 1.31–1.60) if the patient was ICU-admitted, and 1.34 (95% CI: 1.22–1.46) and 1.36 (95% CI: 1.22–1.51) if the patient died. Individuals with a significant person with hospitalized, ICU-admitted, or fatal COVID-19 showed elevated prevalence of depression and anxiety during the entire year after the COVID-19 diagnosis. Interpretation Family members and close friends of critically ill COVID-19 patients show persistently elevated prevalence of depressive and anxiety symptoms.

• Beaumont, Robin N.; Flatley, Christopher; Vaudel, Marc; Wu, Xiaoping; Chen, Jing & Moen, Gunn-Helen Øiseth [Show all 88 contributors for this article] (2023). Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth. Nature Genetics. ISSN 1061-4036. 55, p. 1807–1819. doi: 10.1038/s41588-023-01520-w. Full text in Research Archive Show summary

  A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.

• Kilpi, Fanny; Jones, Hayley E.; Magnus, Maria Christine; Santorelli, Gillian; Schmidt, Lise Kristine Højsgaard & Urhoj, Stine Kjaer [Show all 14 contributors for this article] (2023). Association between perinatal mortality and morbidity and customised and non-customised birthweight centiles in Denmark, Finland, Norway, Wales, and England: comparative, population based, record linkage study. BMJ Medicine. 2(1). doi: 10.1136/bmjmed-2023-000521. Full text in Research Archive
• Øvrebø, Bente; Kjøllesdal, Marte Karoline Råberg; Stea, Tonje Holte; Wills, Andrew Keith; Bere, Elling Tufte & Magnus, Per Minor [Show all 8 contributors for this article] (2023). The influence of immigrant background and parental education on overweight and obesity in 8-year-old children in Norway. BMC Public Health. 23(1). doi: 10.1186/s12889-023-16571-1. Full text in Research Archive Show summary

  Background Little is known about the prevalence of overweight/obesity and socio-economic position (SEP) in children with immigrant background in Scandinavia. The purpose of this study is to examine the prevalence of overweight/obesity by immigrant background among children in Norway and to explore the role of SEP in explaining diferences in weight status. Methods Anthropometric data from 8,858 children (age 8.3 years) from the population-based Norwegian Childhood Growth Study were used. Information about immigrant background, country of origin, and parental education (used as an indicator of SEP) were provided by Statistics Norway. For children with immigrant background, regional background was determined based on country of origin. Prevalence ratios (PR) were estimated for overweight/obesity and weight-to-height-ratio (WHtR)≥0.5 by immigration and regional background, using generalized estimating equation log-binominal models adjusting for sex, age, survey year (model 1), residential area, population density (model 2) and parental education (model 3). Results Children with immigrant background had a higher prevalence of overweight/obesity and WHtR≥0.5 than non-immigrant background children. Adjusted for parental education, children with an immigrant background from Southern and Eastern Europe, Asia except South-Asia, and Africa had a higher prevalence of overweight/ obesity [PR: 1.37 (95% confdence interval (CI): 1.10–1.72), 1.28 (1.05–1.57), 1.47 (1.13–1.91), respectively] than children with a non-immigrant background. Children originating from Asia except South-Asia had a higher prevalence of WHtR≥0.5 (PR: 1.64, CI: 1.25–2.15) compared to non-immigrant background children. The adjustment for parental education did not substantially change the results. Conclusion Children with immigrant background had higher prevalence of overweight/obesity than non-immigrant background children. The diference varied according to region of origin but not substantially according to parental education. There is a need for culturally acceptable preventative measures targeting the parents of immigrant background children.

• Øyri, Linn K. L.; Christensen, Jacob J.; Sebert, Sylvain; Thoresen, Magne; Michelsen, Trond M. & Ulven, Stine M. [Show all 12 contributors for this article] (2023). Maternal prenatal cholesterol levels predict offspring weight trajectories during childhood in the Norwegian Mother, Father and Child Cohort Study. BMC Medicine. 21. doi: 10.1186/s12916-023-02742-9. Full text in Research Archive Show summary

  Background Numerous intrauterine factors may affect the offspring’s growth during childhood. We aimed to explore if maternal and paternal prenatal lipid, apolipoprotein (apo)B and apoA1 levels are associated with offspring weight, length, and body mass index from 6 weeks to eight years of age. This has previously been studied to a limited extent. Methods This parental negative control study is based on the Norwegian Mother, Father and Child Cohort Study and uses data from the Medical Birth Registry of Norway. We included 713 mothers and fathers with or without self-reported hypercholesterolemia and their offspring. Seven parental metabolites were measured by nuclear magnetic resonance spectroscopy, and offspring weight and length were measured at 12 time points. Data were analyzed by linear spline mixed models, and the results are presented as the interaction between parental metabolite levels and offspring spline (age). Results Higher maternal total cholesterol (TC) level was associated with a larger increase in offspring body weight up to 8 years of age (0.03 ≤ Pinteraction ≤ 0.04). Paternal TC level was not associated with change in offspring body weight (0.17 ≤ Pinteraction ≤ 0.25). Higher maternal high-density lipoprotein cholesterol (HDL-C) and apoA1 levels were associated with a lower increase in offspring body weight up to 8 years of age (0.001 ≤ Pinteraction ≤ 0.005). Higher paternal HDL-C and apoA1 levels were associated with a lower increase in offspring body weight up to 5 years of age but a larger increase in offspring body weight from 5 to 8 years of age (0.01 ≤ Pinteraction ≤ 0.03). Parental metabolites were not associated with change in offspring height or body mass index up to 8 years of age (0.07 ≤ Pinteraction ≤ 0.99). Conclusions Maternal compared to paternal TC, HDL-C, and apoA1 levels were more strongly and consistently associated with offspring body weight during childhood, supporting a direct intrauterine effect.

• Llorente, Ignacio Garcia; Lee, Yunsung; Brynildsrud, Ola Brønstad; Eldholm, Vegard; Magnus, Per Minor & Blomfeldt, Anita [Show all 10 contributors for this article] (2023). Tracing the adaptive evolution of SARS-CoV-2 during vaccine roll-out in Norway. Virus Evolution. 10(1). doi: 10.1093/ve/vead081. Full text in Research Archive
• Haftorn, Kristine Løkås; Denault, William Robert Paul; Lee, Yunsung; Page, Christian Magnus; Romanowska, Julia & Lyle, Robert [Show all 12 contributors for this article] (2023). Nucleated red blood cells explain most of the association between DNA methylation and gestational age. Communications Biology. 6. doi: 10.1038/s42003-023-04584-w. Full text in Research Archive Show summary

  Determining if specific cell type(s) are responsible for an association between DNA methylation (DNAm) and a given phenotype is important for understanding the biological mechanisms underlying the association. Our EWAS of gestational age (GA) in 953 newborns from the Norwegian MoBa study identified 13,660 CpGs significantly associated with GA (pBonferroni

• Lu, Li; Hannigan, Laurie John; Brandlistuen, Ragnhild Eek; Nesvåg, Ragnar; Trogstad, Lill & Magnus, Per Minor [Show all 10 contributors for this article] (2023). Mental Distress Among Norwegian Adults During the COVID-19 Pandemic: Predictors in Initial Response and Subsequent Trajectories. International Journal of Public Health. ISSN 1661-8556. 68. doi: 10.3389/ijph.2023.1606164. Full text in Research Archive Show summary

  Objectives: To identify factors associated with change in mental distress at the onset of the COVID-19 pandemic, relative to pre-pandemic levels, and with changes during the following 1.5 years. Methods: The prospective Norwegian Mother, Father and Child Cohort Study collected eight waves of data during the pandemic (March 2020–September 2021) in 105,972 adult participants used for this analyses. A piecewise latent growth model was fitted to identify initial level and longitudinal changes in mental distress. Results: Mental distress peaked at the beginning of the pandemic. Factors associated with initial increases were: medical conditions, living alone, history of psychiatric disorders, lower education, female sex, younger age, and obesity. Being quarantined or infected with SARS-CoV-2 were associated with increasing distress while being vaccinated was associated with reduced mental distress. Conclusion: Having a chronic disease and being quarantined or infected by the SARS-CoV-2 virus were associated with more mental distress during the pandemic. This knowledge is important for planning interventions to support individuals during future pandemics and other societal crises.

• Tverdal, Aage & Magnus, Per Minor (2023). Mortality in Norwegian men and women with an incident myocardial infarction. European Journal of Preventive Cardiology (EJPC). ISSN 2047-4873. 30(16). doi: 10.1093/eurjpc/zwad161. Full text in Research Archive
• Havdahl, Alexandra; Farmer, Cristan; Suren, Pål; Øyen, Anne-Siri; Magnus, Per Minor & Susser, Ezra [Show all 11 contributors for this article] (2023). Attainment and loss of early social-communication skills across neurodevelopmental conditions in the Norwegian Mother, Father and Child Cohort Study. Journal of Child Psychology and Psychiatry. ISSN 0021-9630. doi: 10.1111/jcpp.13792. Full text in Research Archive Show summary

  Background Delays and loss of early-emerging social-communication skills are often discussed as unique to autism. However, most studies of regression have relied on retrospective recall and clinical samples. Here, we examine attainment and loss of social-communication skills in the population-based Norwegian Mother, Father and Child Cohort Study (MoBa). Methods Mothers rated their child's attainment of 10 early-emerging social-communication skills at ages 18 and 36 months (N = 40,613, 50.9% male). Prospectively reported loss was defined as skill presence at 18 months but absence at 36 months. At 36 months, mothers also recalled whether the child had lost social-communication skills. The Norwegian Patient Registry was used to capture diagnoses of Autism Spectrum Disorder (autism) and other neurodevelopmental disabilities (NDDs). Results Delay in at least one skill was observed in 14% of the sample and loss in 5.4%. Recalled loss of social-communication skills was rare (0.86%) and showed low convergence with prospectively reported loss. Delay and especially loss were associated with elevated odds of an autism diagnosis (n = 383) versus no autism diagnosis (n = 40,230; ≥3 skills delayed: OR = 7.09[4.15,12.11]; ≥3 skills lost: OR = 30.66[17.30,54.33]). They were also associated with an increased likelihood of autism compared to some other NDDs. Delay (relative risk [RR] = 4.16[2.08, 8.33]) and loss (RR = 10.00[3.70, 25.00]) associated with increased likelihood of autism versus ADHD, and loss (RR = 4.35[1.28,14.29]), but not delay (RR = 2.00[0.78,5.26]), associated with increased likelihood of autism compared to language disability. Conversely, delay conferred decreased likelihood of autism versus intellectual disability (RR = 0.11[0.06,0.21]), and loss was not reliably associated with likelihood of autism versus intellectual disability (RR = 1.89[0.44,8.33]). Conclusions This population-based study suggests that loss of early social communication skills is more common than studies using retrospective reports have indicated and is observed across several NDD diagnoses (not just autism). Nevertheless, most children with NDD diagnoses showed no reported delay or loss in these prospectively measured skills.

• Shaaban, Ahmed N.; Andersson, Filip; Magnusson, Cecilia; Orsini, Nicola; Caspersen, Ida Henriette & Peña, Sebastian [Show all 9 contributors for this article] (2023). Does misclassification of former tobacco smokers explain the ‘smoker’s paradox’ in the risk of COVID-19? Insights from the Stockholm Public Health Cohort. Scandinavian Journal of Public Health. ISSN 1403-4948. 51(5), p. 735–743. doi: 10.1177/14034948231174279. Full text in Research Archive
• Jami, Eshim S.; Hammerschlag, Anke R.; Sallis, Hannah M.; Qiao, Zhen; Andreassen, Ole & Magnus, Per Minor [Show all 14 contributors for this article] (2023). Do environmental effects indexed by parental genetic variation influence common psychiatric symptoms in childhood? Translational Psychiatry. 13. doi: 10.1038/s41398-023-02348-y. Full text in Research Archive Show summary

  Parental genes may indirectly influence offspring psychiatric outcomes through the environment that parents create for their children. These indirect genetic effects, also known as genetic nurture, could explain individual differences in common internalising and externalising psychiatric symptoms during childhood. Advanced statistical genetic methods leverage data from families to estimate the overall contribution of parental genetic nurture effects. This study included up to 10,499 children, 5990 mother–child pairs, and 6,222 father–child pairs from the Norwegian Mother Father and Child Study. Genome-based restricted maximum likelihood (GREML) models were applied using software packages GCTA and M-GCTA to estimate variance in maternally reported depressive, disruptive, and attention-deficit hyperactivity disorder (ADHD) symptoms in 8-year-olds that was explained by direct offspring genetic effects and maternal or paternal genetic nurture. There was no strong evidence of genetic nurture in this sample, although a suggestive paternal genetic nurture effect on offspring depressive symptoms (variance explained (V) = 0.098, standard error (SE) = 0.057) and a suggestive maternal genetic nurture effect on ADHD symptoms (V = 0.084, SE = 0.058) was observed. The results indicate that parental genetic nurture effects could be of some relevance in explaining individual differences in childhood psychiatric symptoms. However, robustly estimating their contribution is a challenge for researchers given the current paucity of large-scale samples of genotyped families with information on childhood psychiatric outcomes.

• Mørland, Jørg Gustav; Magnus, Per Minor; Vollset, Stein Emil; Leon, David A.; Selmer, Randi Marie & Tverdal, Aage (2023). Associations between serum high-density lipoprotein cholesterol levels and cause-specific mortality in a general population of 345 000 men and women aged 20–79 years. International Journal of Epidemiology. ISSN 0300-5771. 52(4), p. 1257–1267. doi: 10.1093/ije/dyad011. Full text in Research Archive Show summary

  Abstract Background Benefits of elevated high-density lipoprotein cholesterol (HDL-C) levels are challenged by reports demonstrating U-shaped relations between HDL-C levels and all-cause mortality; the association with cause-specific mortality is less studied. Methods A total of 344 556 individuals (20–79 years, 52 % women) recruited from population-based health screening during 1985–2003 were followed until the end of 2018 for all-cause and cause-specific mortality by serum HDL-C level at inclusion of &amp;lt;30, 30–39, 40–49, 50–59, 60–69, 70–79, 80–89, 90–99 and &amp;gt;99 mg/dl (&amp;lt; 0.78, 0.78–1.01, 1.04–1.27, 1.30–1.53, 1.55–1.79, 1.81–2.04, 2.07–2.31, 2.33–2.56, &amp;gt;2.56 mmol/L). Hazard ratios (HRs) were adjusted for sex, age, calendar period, smoking, total cholesterol, triglycerides, systolic blood pressure, physical activity, educational length, body mass index and ill health. Results During a mean follow-up of 22 years, 69 505 individuals died. There were U-shaped associations between HDL-C levels and all-cause, cancer and non-cardiovascular disease/non-cancer mortality (non-CVD/non-cancer), whereas for CVD there was increased risk of death only at lower levels. With HDL-C stratum 50–59 mg/dl (1.30–1.53 mmol/L) as reference, HRs [95% confidence intervals (CIs)] for levels &amp;gt;99 mg/dl (&amp;gt;2.56 mmol/L) were 1.32 (1.21–1.43), 1.05 (0.89–1.24), 1.26 (1.09–1.46) and 1.68 (1.48–1.90) for all–cause, CVD, cancer and non–CVD/non–cancer mortality, respectively. For HDL-C levels &amp;lt;30 mg/dl (0.78 mmol/L), the corresponding HRs (95% CIs) were 1.30 (1.24–1.36), 1.55 (1.44–1.67), 1.14 (1.05–1.23) and 1.19 (1.10–1.29). The mortality from alcoholic liver disease, cancers of mouth-oesophagus-liver, chronic liver diseases, chronic obstructive pulmonary disease, accidents and diabetes increased distinctly with increasing HDL-C above the reference level. HDL-C levels lower than the reference level were mainly associated with increased mortality of ischaemic heart disease (IHD), other CVDs, stomach cancer and diabetes. Conclusions Higher HDL-C levels were associated with increased mortality risk of several diseases which also have been associated with heavy drinking, and lower HDL-C levels were associated with increased mortality from IHD, other CVDs, gastric cancer and diabetes.

• Caspersen, Ida Henriette; Juvet, Lene Kristine; Feiring, Berit; Laake, Ida; Robertson, Anna Hayman & Mjaaland, Siri [Show all 8 contributors for this article] (2023). Menstrual disturbances in 12- to 15-year-old girls after one dose of COVID-19 Comirnaty vaccine: Population-based cohort study in Norway. Vaccine. ISSN 0264-410X. 41(2), p. 614–620. doi: 10.1016/j.vaccine.2022.11.068. Full text in Research Archive
• Solé-Navais, Pol; Flatley, Christopher; Steinthorsdottir, Valgerdur; Vaudel, Marc; Juodakis, Julius & Chen, Jing [Show all 85 contributors for this article] (2023). Genetic effects on the timing of parturition and links to fetal birth weight. Nature Genetics. ISSN 1061-4036. 55, p. 559–567. doi: 10.1038/s41588-023-01343-9. Full text in Research Archive Show summary

  The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n = 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed seven associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n = 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal–fetal relationship between gestational duration and birth weight.

• Wootton, Robyn E; Lawn, Rebecca B.; Magnus, Maria C.; Treur, Jorien L.; Corfield, Elizabeth C. & Njølstad, Pål Rasmus [Show all 14 contributors for this article] (2023). Associations between health behaviours, fertility and reproductive outcomes: triangulation of evidence in the Norwegian Mother, Father and Child Cohort Study (MoBa). BMC Medicine. 21. doi: 10.1186/s12916-023-02831-9. Full text in Research Archive Show summary

  Background Guidance to improve fertility includes reducing alcohol and caffeine consumption, achieving healthy weight-range and stopping smoking. Advice is informed by observational evidence, which is often biased by confounding. Methods This study primarily used data from a pregnancy cohort, the Norwegian Mother, Father and Child Cohort Study. First, we conducted multivariable regression of health behaviours (alcohol and caffeine consumption, body-mass index (BMI), and smoking) on fertility outcomes (e.g. time to conception) and reproductive outcomes (e.g. age at first birth) (n = 84,075 females, 68,002 males), adjusting for birth year, education and attention-deficit and hyperactive-impulsive (ADHD) traits. Second, we used individual-level Mendelian randomisation (MR) to explore possible causal effects of health behaviours on fertility/reproductive outcomes (n = 63,376 females, 45,460 males). Finally, we performed summary-level MR for available outcomes in UK Biobank (n = 91,462–1,232,091) and controlled for education and ADHD liability using multivariable MR. Results In multivariable regression analyses, higher BMI associated with fertility (longer time to conception, increased odds of infertility treatment and miscarriage), and smoking was associated with longer time to conception. In individual-level MR analyses, there was strong evidence for effects of smoking initiation and higher BMI on younger age at first birth, of higher BMI on increased time to conception, and weak evidence for effects of smoking initiation on increased time to conception. Age at first birth associations were replicated in summary-level MR analysis; however, effects attenuated using multivariable MR. Conclusions Smoking behaviour and BMI showed the most consistent associations for increased time to conception and a younger age at first birth. Given that age at first birth and time to conception are positively correlated, this suggests that the mechanisms for reproductive outcomes are distinct to the mechanisms acting on fertility outcomes. Multivariable MR suggested that effects on age at first birth might be explained by underlying liability to ADHD and education.

• Blix, Kristine; Laake, Ida; Juvet, Lene Kristine; Robertson, Anna Hayman; Caspersen, Ida Henriette & Mjaaland, Siri [Show all 10 contributors for this article] (2023). Unexpected vaginal bleeding and COVID-19 vaccination in nonmenstruating women. Science Advances. 9(38). doi: 10.1126/sciadv.adg1391. Full text in Research Archive
• Solberg, Berit Skretting; Kvalvik, Liv Grimstvedt; Instanes, Johanne Telnes; Hartman, Catharina A.; Klungsøyr, Kari & Li, Lin [Show all 20 contributors for this article] (2023). Maternal Fiber Intake During Pregnancy and Development of Attention-Deficit/Hyperactivity Disorder Symptoms Across Childhood: The Norwegian Mother, Father, and Child Cohort Study. Biological Psychiatry. ISSN 0006-3223. 95(9), p. 839–848. doi: 10.1016/j.biopsych.2023.12.017. Full text in Research Archive Show summary

  Background Epidemiological studies suggest that maternal diet quality during pregnancy may influence the risk of neurodevelopmental disorders in offspring. Here, we investigated associations between maternal intake of dietary fiber and attention-deficit/hyperactivity disorder (ADHD) symptoms in early childhood. Methods We used longitudinal data of up to 21,852 mother-father-child trios (49.2% female offspring) from MoBa (the Norwegian Mother, Father, and Child Cohort Study). The relationships between maternal fiber intake during pregnancy and offspring ADHD symptoms at ages 3, 5, and 8 years were examined using 1) multivariate regression (overall levels of ADHD symptoms), 2) latent class analysis (subclasses of ADHD symptoms by sex at each age), and 3) latent growth curves (longitudinal change in offspring ADHD symptoms). Covariates were ADHD polygenic scores in child and parents, total energy intake and energy-adjusted sugar intake, parental ages at birth of the child, and sociodemographic factors. Results Higher maternal prenatal fiber intake was associated with lower offspring ADHD symptom scores at all ages (Bage3 = −0.14 [95% CI, −0.18 to −0.10]; Bage5 = −0.14 [95% CI, −0.19 to −0.09]; Bage8 = −0.14 [95% CI, −0.20 to −0.09]). Of the derived low/middle/high subclasses of ADHD symptoms, fiber was associated with lower risk of belonging to the middle subclass for boys and girls and to the high subclass for girls only (middle: odds ratioboys 0.91 [95% CI, 0.86 to 0.97]/odds ratiogirls 0.86 [95% CI, 0.81 to 0.91]; high: odds ratiogirls 0.82 [95% CI, 0.72 to 0.94]). Maternal fiber intake and rate of change in child ADHD symptoms across ages were not associated. Conclusions Low prenatal maternal fiber intake may increase symptom levels of ADHD in offspring during childhood, independently of genetic predisposition to ADHD, unhealthy dietary exposures, and sociodemographic factors.

• Shaaban, A.N.; Andersson, F.; Peña, S.; Caspersen, Ida Henriette; Magnusson, C. & Orsini, N. [Show all 10 contributors for this article] (2023). The Association Between Tobacco Use and Risk of COVID-19 Infection and Clinical Outcomes in Sweden: A Population-Based Study. International Journal of Public Health. ISSN 1661-8556. 68. doi: 10.3389/ijph.2023.1606175. Full text in Research Archive
• He, Jian-Rong; Yu, Yongfu; Fang, Fang; Gissler, Mika; Magnus, Per Minor & László, Krisztina D. [Show all 19 contributors for this article] (2023). Evaluation of Maternal Infection During Pregnancy and Childhood Leukemia Among Offspring in Denmark. JAMA Network Open. 6(2). doi: 10.1001/jamanetworkopen.2023.0133. Full text in Research Archive
• Romanowska, Julia; Nustad, Haakon Egdetveit; Page, Christian Magnus; Denault, William Robert Paul; Lee, Yunsung & Magnus, Maria Christine [Show all 15 contributors for this article] (2023). The X-factor in ART: does the use of assisted reproductive technologies influence DNA methylation on the X chromosome? Human Genomics. ISSN 1473-9542. 17(1). doi: 10.1186/s40246-023-00484-6. Full text in Research Archive Show summary

  Background Assisted reproductive technologies (ART) may perturb DNA methylation (DNAm) in early embryonic development. Although a handful of epigenome-wide association studies of ART have been published, none have investigated CpGs on the X chromosome. To bridge this knowledge gap, we leveraged one of the largest collections of mother–father–newborn trios of ART and non-ART (natural) conceptions to date to investigate sex-specific DNAm differences on the X chromosome. The discovery cohort consisted of 982 ART and 963 non-ART trios from the Norwegian Mother, Father, and Child Cohort Study (MoBa). To verify our results from the MoBa cohort, we used an external cohort of 149 ART and 58 non-ART neonates from the Australian ‘Clinical review of the Health of adults conceived following Assisted Reproductive Technologies’ (CHART) study. The Illumina EPIC array was used to measure DNAm in both datasets. In the MoBa cohort, we performed a set of X-chromosome-wide association studies (‘XWASs’ hereafter) to search for sex-specific DNAm differences between ART and non-ART newborns. We tested several models to investigate the influence of various confounders, including parental DNAm. We also searched for differentially methylated regions (DMRs) and regions of co-methylation flanking the most significant CpGs. Additionally, we ran an analogous model to our main model on the external CHART dataset. Results In the MoBa cohort, we found more differentially methylated CpGs and DMRs in girls than boys. Most of the associations persisted after controlling for parental DNAm and other confounders. Many of the significant CpGs and DMRs were in gene-promoter regions, and several of the genes linked to these CpGs are expressed in tissues relevant for both ART and sex (testis, placenta, and fallopian tube). We found no support for parental DNAm-dependent features as an explanation for the observed associations in the newborns. The most significant CpG in the boys-only analysis was in UBE2DNL, which is expressed in testes but with unknown function. The most significant CpGs in the girls-only analysis were in EIF2S3 and AMOT. These three loci also displayed differential DNAm in the CHART cohort. Conclusions Genes that co-localized with the significant CpGs and DMRs associated with ART are implicated in several key biological processes (e.g., neurodevelopment) and disorders (e.g., intellectual disability and autism). These connections are particularly compelling in light of previous findings indicating that neurodevelopmental outcomes differ in ART-conceived children compared to those naturally conceived.

• Caspersen, Ida Henriette; Trogstad, Lill; Galanti, Maria Rosaria; Karvonen, Sakari; Peña, Sebastián & Shaaban, Ahmed Nabil [Show all 8 contributors for this article] (2023). Current tobacco use and SARS-CoV-2 infection in two Norwegian population-based cohorts. BMC Public Health. 23, p. 1–9. doi: 10.1186/s12889-023-15822-5. Full text in Research Archive Show summary

  Background Clear evidence of an increased risk for SARS-CoV-2 infection among smokers has not been established. We aimed to investigate associations between cigarette smoking or use of snus (snuff) and other nicotine-containing products and a positive SARS-CoV-2 test, taking test behavior into account. Methods Current tobacco use and testing behavior during the pandemic were recorded by adult participants from the Norwegian Mother, Father and Child Cohort Study and The Norwegian Influenza Pregnancy Cohort. SARS-CoV-2 infection status was obtained from The Norwegian Surveillance System for Communicable Diseases (MSIS) in May 2021 (n = 78,860) and antibody measurements (n = 5581). We used logistic regression models stratified by gender and adjusted for age, education, region, number of household members, and work situation. Results Snus use was more common among men (26%) than women (9%) and more prevalent than cigarette smoking. We found no clear associations between cigarette smoking or snus and a COVID-19 diagnosis among men. Associations among women were conflicting, indicating that cigarette smoke was negatively associated with a diagnosis (OR 0.51, 95% CI 0.35, 0.75), while no association was found for snus use (OR 1.07, 95% CI 0.86, 1.34). Compared with non-users of tobacco, both cigarette smokers and snus users had increased odds of being tested for SARS-CoV-2. Conclusions Cigarette smoking, but not snus use, was negatively associated with SARS-CoV-2 infection in women. The lack of an association between snus use and SARS-CoV-2 infection in this population with prevalent snus use does not support the hypothesis of a protective effect of nicotine.

• Haftorn, Kristine Løkås; Romanowska, Julia; Lee, Yunsung; Page, Christian Magnus; Magnus, Per Minor & Håberg, Siri Eldevik [Show all 9 contributors for this article] (2023). Stability selection enhances feature selection and enables accurate prediction of gestational age using only five DNA methylation sites. Clinical Epigenetics. 15. doi: 10.1186/s13148-023-01528-3. Full text in Research Archive Show summary

  Background: DNA methylation (DNAm) is robustly associated with chronological age in children and adults, and gestational age (GA) in newborns. This property has enabled the development of several epigenetic clocks that can accurately predict chronological age and GA. However, the lack of overlap in predictive CpGs across different epigenetic clocks remains elusive. Our main aim was therefore to identify and characterize CpGs that are stably predictive of GA. Results: We applied a statistical approach called 'stability selection' to DNAm data from 2138 newborns in the Norwegian Mother, Father, and Child Cohort study. Stability selection combines subsampling with variable selection to restrict the number of false discoveries in the set of selected variables. Twenty-four CpGs were identified as being stably predictive of GA. Intriguingly, only up to 10% of the CpGs in previous GA clocks were found to be stably selected. Based on these results, we used generalized additive model regression to develop a new GA clock consisting of only five CpGs, which showed a similar predictive performance as previous GA clocks (R2 = 0.674, median absolute deviation = 4.4 days). These CpGs were in or near genes and regulatory regions involved in immune responses, metabolism, and developmental processes. Furthermore, accounting for nonlinear associations improved prediction performance in preterm newborns. Conclusion: We present a methodological framework for feature selection that is broadly applicable to any trait that can be predicted from DNAm data. We demonstrate its utility by identifying CpGs that are highly predictive of GA and present a new and highly performant GA clock based on only five CpGs that is more amenable to a clinical setting. Keywords: Cord blood; DNA methylation; Epigenetic clock; Epigenetics; Feature selection; Gestational age; Illumina MethylationEPIC BeadChip; MBRN; MoBa; Stability selection.

• Tran, Trung; Vaage, Eline Benno; Mehta, Adi; Chopra, Adity; Tietze, Lisa & Kolderup, Heidi Anette [Show all 40 contributors for this article] (2022). Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants. npj Vaccines. 7(1). doi: 10.1038/s41541-022-00586-7. Full text in Research Archive Show summary

  Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 serum samples. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.

• Barlinn, Regine; Dudman, Susanne Gjeruldsen; Rollag, Halvor; Trogstad, Lill; Lindstrøm, Jonas Christoffer & Magnus, Per Minor (2022). Maternal cytomegalovirus infection and delayed language development in children at 3 years of age-a nested case-control study in a large population-based pregnancy cohort. PLOS ONE. 17(12). doi: 10.1371/journal.pone.0278623. Full text in Research Archive Show summary

  Introduction Maternal cytomegalovirus (CMV) infection in pregnancy may result in vertical transmission of CMV to the child. Long-term effects of congenital CMV infection include visual, cognitive as well as neurological impairment. The aim of this study was to estimate the odds ratios for CMV seropositivity and seroconversion in mothers, with and without delayed language development in 3 year old children, nested within a large cohort. Material and methods The Norwegian Mother, Father and Child Cohort Study (MoBa) is a prospective population-based pregnancy cohort that includes 95 200 mothers and 114 500 children. Blood samples were obtained from mothers during pregnancy weeks 17 or 18 in pregnancy and after birth. We included 300 women from MoBa with children suffering from delayed language development at three years of age, based on validated questionnaires. Within the cohort, 1350 randomly selected women were included as controls to perform a nested case-control study. The cases and controls were tested for CMV IgG antibodies by an enzyme-linked immunosorbent assay. Results Among mothers of cases, 63.2% were CMV-IgG positive in the sample at birth, as compared to 55.9% among controls; OR 1.36, (95% CI; 1.05 to 1.76). Also, among case mothers, 8/118 (6.8%) initially seronegative cases, seroconverted. Among initially seronegative controls, seroconversion occurred in 23/618 (3.7%) mothers. The OR for seroconversion in cases as compared to control mothers was 1.88 (CI; 0.82 to 4.31), thus not statistically significant different. Conclusion This study shows a higher risk of delayed language development at three years of age in children born by mothers seropositive for CMV, compared to children born from seronegative mothers.

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• Vartiainen, Pekka; Haapaniemi, Hele; Lee, Yunsung; Magnus, Maria Christine; Hartonen, Tuomo & Detrois, Kira [Show all 31 contributors for this article] (2026). Infant respiratory syncytial virus and childhood asthma: a nationwide registry-based, sibling-controlled, and genome-wide association study. medRxiv. doi: 10.64898/2026.07.17.26351934. Full text in Research Archive Show summary

  Abstract Background Early-life respiratory syncytial virus (RSV) infection is associated with childhood recurrent wheeze or asthma (RW/A), but causality and shared genetic liability remain unclear. Methods We combined Finnish nationwide registries and Nordic genetic cohorts. First, in 965 312 Finnish children born between 1998 and 2014, we defined severe RSV as RSV hospitalisation before age 1 year, and recurrent wheezing or asthma (RW/A) as inhaled medication reimbursement between ages 1 and 7 years, and compared medication and eosinophil trajectories by RSV history. Second, we assessed familial confounding in 527 776 full siblings and 15 667 RW/A- discordant pairs. Third, we performed a genome-wide association study (GWAS) of RSV susceptibility with meta-analysis across six Nordic cohorts (3 107 cases, 92 091 controls) and two-sample Mendelian randomisation (2SMR) using 155 asthma-associated variants. Findings RSV-associated RW/A showed higher inhaled medication use at ages 1–2 years but lower use after age 5, and lower mean blood eosinophils (0·341 vs 0·398×10□/L; p=0·008) than RW/A without RSV hospitalisation. In RW/A-discordant sibling pairs, RSV hospitalisation was associated with RW/A (OR 2·8; 95% CI 2·4–3·2), while unaffected siblings also had elevated RW/A prevalence. GWAS identified an RSV association at APBB1IP (rs787036; β=0·209; p=8·80×10 - □). 2SMR provided no evidence that asthma genetic liability influenced RSV susceptibility. Interpretation The RSV–asthma association is unlikely to be explained by shared genetic or environmental factors, and RSV-associated RW/A shows a distinct trajectory. These findings help prioritise long-term outcomes for RSV prevention trials and monitoring. Funding Päivikki and Sakari Sohlberg Foundation, Foundation for Pediatric Research, Sigrid Jusélius Foundation, Orion Research Foundation, the Research Council of Norway.

• Magnus, Maria Christine; Lee, Yunsung; Carlsen, Ellen Øen; Arge, Lise Andrea; Jugessur, Astanand & Kvalvik, Liv Grimstvedt [Show all 11 contributors for this article] (2025). Correction: Parental epigenetic age acceleration and risk of adverse birth outcomes: the Norwegian mother, father and child cohort study. BMC Medicine. 23(1). doi: 10.1186/s12916-024-03824-y. Full text in Research Archive
• Håberg, Siri Eldevik & Magnus, Per Minor (2025). Nysgjerrige på: fruktbarhetens mysterier. doi: https:/shows.acast.com/nysgjerrige-norge/episodes/nysgjerrige-pa-fruktbarhetens-mysterier. Full text in Research Archive
• Nyquist, Cecilie Bjertness; Torgersen, Leila; Davidsen, Linda; Diseth, Trond Haaken; Magnus, Per Minor & Biele, Guido [Show all 7 contributors for this article] (2025). Reply to letter of concerns from Banos et al. European Child and Adolescent Psychiatry. ISSN 1018-8827. doi: 10.1007/s00787-025-02690-0. Full text in Research Archive
• Ghantous, Akram; Nusslé, Semira Gonseth; Nassar, Farah J.; Spitz, Natalia; Novoloaca, Alexei & Krali, Olga [Show all 31 contributors for this article] (2024). Epigenome-wide analysis across the development span of pediatric acute lymphoblastic leukemia: backtracking to birth. Molecular Cancer. 23(1). doi: 10.1186/s12943-024-02118-4. Full text in Research Archive
• Helgeland, Øyvind; Vaudel, Marc; Sole-Navais, Pol; Flatley, Christopher; Juodakis, Julius & Bacelis, Jonas [Show all 18 contributors for this article] (2024). Correction to: Characterization of the genetic architecture of infant and early childhood body mass index (Nature Metabolism, (2022), 4, 3, (344-358), 10.1038/s42255-022-00549-1). Nature Metabolism. 6(2), p. 378–378. doi: 10.1038/s42255-024-01004-z. Full text in Research Archive
• Askelund, Adrian Dahl; Wootton, Robyn E; Torvik, Fartein Ask; Lawn, Rebecca B.; Ask, Helga & Corfield, Elizabeth Claire [Show all 15 contributors for this article] (2024). Assessing causal links between age at menarche and adolescent mental health: triangulation of evidence from a Registered Report. Full text in Research Archive Show summary

  The timing of puberty may influence adolescent mental health. Earlier age at menarche has been associated with depression in adolescents. Previous research suggests that this relationship may be causal, but replication and an investigation of whether this effect extends to other mental health domains is warranted. In this Registered Report, we used a new wave of data (N=13,398) from the Norwegian Mother, Father, and Child Cohort Study. We combined multiple regression, one- and two-sample Mendelian randomisation (MR), and negative control analyses (using pre-pubertal symptoms as outcomes) to assess causal links between age at menarche and adolescent mental health. As hypothesised, earlier age at menarche was associated with elevated depressive symptoms in early adolescence based on multiple regression (β = -0.11, 95% CI [-0.12, -0.09], p one-tailed = 0.01). One-sample MR analyses suggested that this relationship may be causal (β = -0.07, 95% CI [-0.13, 0.00], p one- tailed = 0.03). There was also some evidence of a causal relationship with depression diagnoses during adolescence based on one-sample MR (OR = 0.74, 95% CI [0.54, 1.01], p one-tailed = 0.03), corresponding to a 29% increase in the odds of receiving a depression diagnosis with each earlier year of menarche. Negative control and two-sample MR sensitivity analyses were broadly consistent with this pattern of results. Meanwhile, we found little evidence of effects on other domains of mental health after accounting for co-occurring depression and other confounding. Age at menarche affected adolescent depression, but not other domains of mental health. Our findings suggest that earlier age at menarche is linked to problems in specific domains rather than adolescent mental health in general.

• Hart, Rannveig Kaldager; Håberg, Siri Eldevik; Magnus, Per Minor & Kravdal, Øystein (2023). Hvorfor faller fruktbarheten så dramatisk? Full text in Research Archive
• Belanger, Sissel Marguerite; Hauge, Lars Johan; Reneflot, Anne; Øien-Ødegaard, Carine; Christiansen, Solveig Tobie Glestad & Magnus, Per Minor [Show all 7 contributors for this article] (2023). General practitioner consultations for mental health reasons prior to and following bereavement by suicide. Full text in Research Archive
• Tverdal, Aage & Magnus, Per Minor (2023). Diabetes and Parkinson’s disease. European Journal of Epidemiology (EJE). ISSN 0393-2990. doi: 10.1007/s10654-023-01054-9. Full text in Research Archive
• Lee, Yunsung; Gjerdevik, Miriam; Jugessur, Astanand; Gjessing, Håkon Kristian; Corfield, Elizabeth Claire & Havdahl, Alexandra [Show all 10 contributors for this article] (2023). Parent-of-origin effects on childhood asthma. Full text in Research Archive
• Solé-Navais, Pol; Flatley, Christopher; Steinthorsdottir, Valgerdur; Vaudel, Marc; Juodakis, Julius & Chen, Jing [Show all 85 contributors for this article] (2023). Author Correction: Genetic effects on the timing of parturition and links to fetal birth weight (Nature Genetics, (2023), 55, 4, (559-567), 10.1038/s41588-023-01343-9). Nature Genetics. ISSN 1061-4036. doi: 10.1038/s41588-023-01412-z. Full text in Research Archive
• Tran, Trung; Vaage, Eline Benno; Mehta, Adi; Chopra, Adity; Tietze, Lisa & Kolderup, Heidi Anette [Show all 40 contributors for this article] (2023). Author Correction: Titers of antibodies against ancestral SARS-CoV-2 correlate with levels of neutralizing antibodies to multiple variants (npj Vaccines, (2022), 7, 1, (174), 10.1038/s41541-022-00586-7). npj Vaccines. 8(1). doi: 10.1038/s41541-023-00600-6. Full text in Research Archive
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• Corfield, Elizabeth Claire; Frei, Oleksandr; Shadrin, Alexey; Rahman, Zillur; Lin, Aihua & Athanasiu, Lavinia [Show all 26 contributors for this article] (2022). The Norwegian Mother, Father, and Child cohort study (MoBa) genotyping data resource: the MoBaPsychGen_v1 pipeline. Full text in Research Archive
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• Corfield, Elizabeth Claire; Frei, Oleksandr; Shadrin, Alexey; Rahman, Zillur; Lin, Aihua & Athanasiu, Lavinia [Show all 26 contributors for this article] (2022). The Norwegian Mother, Father, and Child cohort study (MoBa) genotyping data resource: MoBaPsychGen pipeline v.1. Cold Spring Harbor Laboratory Press (CSHL). doi: 10.1101/2022.06.23.496289. Full text in Research Archive Show summary

  Background: The Norwegian Mother, Father, and Child Cohort Study (MoBa) is a population-based pregnancy cohort, which includes approximately 114,500 children, 95,200 mothers, and 75,200 fathers. Genotyping of MoBa has been conducted through multiple research projects, spanning several years; using varying selection criteria, genotyping arrays, and genotyping centres. MoBa contains numerous interrelated families, which necessitated the implementation of a family-based quality control (QC) pipeline that verifies and accounts for diverse types of relatedness. Methods: The MoBaPsychGen pipeline, comprising pre-imputation QC, phasing, imputation, and post-imputation QC, was developed based on current best-practice protocols and implemented to account for the complex structure of the MoBa genotype data. The pipeline includes QC on both single nucleotide polymorphism (SNP) and individual level. Phasing and imputation were performed using the publicly available Haplotype Reference Consortium release 1.1 panel as a reference. Information from the Medical Birth Registry of Norway and MoBa questionnaires were used to identify biological sex, year of birth, reported parent-offspring (PO) relationships, and multiple births (only available in the offspring generation). Results: In total, 207,569 unique individuals (90% of the unique individuals included in the study) and 6,981,748 SNPs passed the MoBaPsychGen pipeline. The relatedness checks performed throughout the pipeline allowed identification of within-generation and across-generation first-degree, second-degree, and third-degree relatives. The individuals passing post-imputation QC comprised 64,471 families ranging in size from singletons to 84 unique individuals (singletons are included as families as other family members may not have been genotyped, imputed, or passed post-imputation QC). The relationships identified include 287 monozygotic twin pairs, 22,884 full siblings, 117,004 PO pairs, 23,299 second-degree relative pairs, and 10,828 third-degree relative pairs. Discussion: MoBa contains a highly complex relatedness structure, with a variety of family structures including singletons, PO duos, full (mother, father, child) PO trios, nuclear families, blended families, and extended families. The availability of robustly quality-controlled genetic data for such a large cohort with a unique extended family structure will allow many novel research questions to be addressed. Furthermore, the MoBaPsychGen pipeline has potential utility in similar cohorts.

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