Tormod Rogne

• Thorkildsen, Marianne Thorkildsen; Gustad, Lise Tuset; Åsvold, Bjørn Olav; Mohus, Randi Marie; Ellervik, Christina & Teumer, Alexander [Show all 11 contributors for this article] (2026). Thyroid function and risk of sepsis: a population-based prospective cohort study with traditional and genetic epidemiological analyses. Frontiers in Endocrinology. 17. doi: 10.3389/fendo.2026.1852413. Full text in Research Archive
• 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.

• Zhuo, Haoran; Rogne, Tormod & Liew, Zeyan (2025). A sibling study of the prenatal and perinatal risks for cerebral palsy. Pediatric Research. ISSN 0031-3998. doi: 10.1038/s41390-025-04055-4. Full text in Research Archive
• Stensrud, Vilde Hatlevoll; Rogne, Tormod; Flatby, Helene Marie; Mohus, Randi Marie; Gustad, Lise Tuset & Nilsen, Tom Ivar Lund (2025). Examining socioeconomic differences in sepsis risk and mediation by modifiable factors: a Mendelian randomization study. BMC Infectious Diseases. 25(1). doi: 10.1186/s12879-025-11130-y. Full text in Research Archive Show summary

  Background Educational attainment is inversely related to sepsis risk, but the causal nature is still unclear. We therefore conducted the first Mendelian randomization (MR) study of genetically predicted educational attainment on sepsis that also uses a within-family genetic instrument for education. To further explore possible mechanistic pathways that can inform strategies to reduce sepsis risk, we examined the mediating effects of factors that are modifiable or can be prevented. Methods The association between genetically predicted educational attainment and sepsis was estimated using summary-level data from recent genome-wide association studies. Possible bias due to population stratification, dynastic effects, and assortative mating in the genetic instrument for education was evaluated using summary-level data from a within-sibship genome-wide association study. We used inverse variance weighted MR analysis to estimate the effect of one standard deviation increase in years of education on sepsis risk. The robustness of the findings was assessed in sensitivity analyses, applying weighted median, weighted mode, and MR Egger regression. Finally, we applied multivariable MR analyses to estimate the mediating effects of smoking initiation, alcohol consumption, body mass index, high-density lipoprotein (HDL)-cholesterol, systolic blood pressure and type 2 diabetes. Results For each standard deviation increase in genetically predicted educational attainment (3.4 years), the odds ratio (OR) for sepsis was 0.72 (95% confidence interval (CI) 0.66 to 0.78). The results of the analysis using the within-sibship genetic instrument and other sensitivity analyses were in line with this finding: within-sibship OR 0.88 (95% CI 0.64 to 1.18), weighted median OR 0.70 (95% CI 0.62 to 0.80), weighted mode OR 0.70 (95% CI 0.43 to 1.13), and MR Egger OR 0.65 (95% CI 0.50 to 0.85). The mediation analysis showed that 56% of the effect of educational attainment on sepsis risk can be explained by modifiable or preventable factors. Conclusions Higher educational attainment is strongly associated with a reduced risk of sepsis, pointing to important socioeconomic differences in this disease. The results also suggest that interventions targeting modifiable or preventable factors could contribute to reducing the socioeconomic differences in sepsis risk.

• Liyanarachi, Kristin Vardheim; Flatby, Helene Marie; Hallan, Stein Ivar; Åsvold, Bjørn Olav; Damås, Jan Kristian & Rogne, Tormod (2025). Uromodulin and Risk of Upper Urinary Tract Infections: A Mendelian Randomization Study. American Journal of Kidney Diseases. ISSN 0272-6386. doi: 10.1053/j.ajkd.2024.11.007. Full text in Research Archive
• Harpe, Roxane de La; Rogne, Tormod; Nyberg, Michael; Cronjé, Héléne T.; Burgess, Stephen & Karhunen, Ville [Show all 7 contributors for this article] (2025). Associations of Genetically Predicted NPR3 and NPR2 Perturbation and Preeclampsia Risk: A Two-Sample Mendelian Randomization Analysis. International Journal of Hypertension. ISSN 2090-0384. 2025(1). doi: 10.1155/ijhy/9972031. Full text in Research Archive
• Rogne, Tormod & Gill, Dipender (2025). Adverse Pregnancy Outcomes and Coronary Artery Disease Risk: A Negative Control Mendelian Randomization Study. Circulation. ISSN 0009-7322. 151(2), p. 193–195. doi: 10.1161/CIRCULATIONAHA.124.070509. Full text in Research Archive
• Rogne, Tormod; Gill, Dipender; Liew, Zeyan; Shi, Xiaoting; Stensrud, Vilde & Nilsen, Tom Ivar Lund [Show all 7 contributors for this article] (2024). Mediating Factors in the Association of Maternal Educational Level with Pregnancy Outcomes: A Mendelian Randomization Study. JAMA Network Open. 7(1), p. E2351166–E2351166. doi: 10.1001/jamanetworkopen.2023.51166. Full text in Research Archive Show summary

  IMPORTANCE Lower educational attainment is associated with increased risk of adverse pregnancy outcomes, but it is unclear which pathways mediate this association. OBJECTIVE To investigate the association between educational attainment and pregnancy outcomes and the proportion of this association that is mediated through modifiable cardiometabolic risk factors. DESIGN, SETTING, AND PARTICIPANTS In this 2-sample mendelian randomization (MR) cohort study, uncorrelated (R2 < 0.01) single-nucleotide variants (formerly single-nucleotide polymorphisms) associated with the exposure (P < 5 × 10−8) and mediators and genetic associations with the pregnancy outcomes from genome-wide association studies were extracted. All participants were of European ancestry and were largely from Finland, Iceland, the United Kingdom, or the US. The inverse variance–weighted method was used in the main analysis, and the weighted median, weighted mode, and MR Egger regression were used in sensitivity analyses. In mediation analyses, the direct effect of educational attainment estimated in multivariable MR was compared with the total effect estimated in the main univariable MR analysis. Data were extracted between December 1, 2022, and April 30, 2023. EXPOSURE Genetically estimated educational attainment. The mediators considered were genetically estimated type 2 diabetes, body mass index, smoking, high-density lipoprotein cholesterol level, and systolic blood pressure. MAIN OUTCOMES AND MEASURES Ectopic pregnancy, hyperemesis gravidarum, gestational diabetes, preeclampsia, preterm birth, and offspring birth weight. RESULTS The analyses included 3 037 499 individuals with data on educational attainment, and those included in studies on pregnancy outcomes ranged from 141 014 for ectopic pregnancy to 270 002 with data on offspring birth weight. Each SD increase in genetically estimated educational attainment (ie, 3.4 years) was associated with an increased birth weight of 42 (95% CI, 28-56) g and an odds ratio ranging from 0.53 (95% CI, 0.46-0.60) for ectopic pregnancy to 0.81 (95% CI, 0.71-0.93) for preeclampsia. The combined proportion of the association that was mediated by the 5 cardiometabolic risk factors ranged from −17% (95% CI, −46% to 26%) for hyperemesis gravidarum to 78% (95% CI, 10%-208%) for preeclampsia. Sensitivity analyses accounting for pleiotropy were consistent with the main analyses. CONCLUSIONS AND RELEVANCE In this MR cohort study, intervening for type 2 diabetes, body mass index, smoking, high-density lipoprotein cholesterol level, and systolic blood pressure may lead to reductions in several adverse pregnancy outcomes associated with lower levels of education. Such public health interventions would serve to reduce health disparities attributable to social inequalities.

• Flatby, Helene Marie; Ravi, Anuradha; Liyanarachi, Kristin Vardheim; Afset, Jan Egil; Rasheed, Humaira & Brumpton, Ben Michael [Show all 12 contributors for this article] (2024). A Genome-wide Association Study of Susceptibility to Upper Urinary Tract Infections. Journal of Infectious Diseases. ISSN 0022-1899. 230(6), p. e1334–e1343. doi: 10.1093/infdis/jiae231. Full text in Research Archive Show summary

  Background Our goal was to identify genetic and modifiable risk factors for upper urinary tract infections (UTIs). Methods We used data from UK Biobank, the Trøndelag Health Study, and the Michigan Genomics Initiative to conduct genome-wide association studies and sex-stratified analyses on upper UTI. Mendelian randomization (MR) analyses were conducted to examine potential causal relationships between cardiometabolic risk factors and upper UTIs. Results One genome-wide significant (P ≤ 5E-08) locus was associated with the susceptibility to upper UTI, located near TSN in the female-only analysis. Additionally, we identified suggestive (P ≤ 5E-06) loci near DNAI3 for females, SCAMP1−AS1 for males, and near TSN, LINC00603, and HLA-DQA2 for both sexes. In MR analyses, higher genetically predicted lifetime smoking scores were associated with an increased risk of developing upper UTI for females and both sexes (odds ratio [OR], 4.84, P = 4.50E-06 and OR, 2.79, P = 3.02E-05, respectively). Conclusions We found t

• Shi, Xiaoting; Wallach, Joshua D.; Ma, Xiaomei & Rogne, Tormod (2024). Autoimmune Diseases and Risk of Non-Hodgkin Lymphoma: A Mendelian Randomisation Study. Cancer Medicine. 13(21). doi: 10.1002/cam4.70327. Full text in Research Archive Show summary

  Background Non-Hodgkin lymphoma (NHL) is one of the most common haematologic malignancies in the world. Despite substantial efforts to identify causes and risk factors for NHL, its aetiology is largely unclear. Autoimmune diseases have long been considered potential risk factors for NHL. We carried out Mendelian randomisation (MR) analyses to examine whether genetically predicted susceptibility to ten autoimmune diseases (Behçet's disease, coeliac disease, dermatitis herpetiformis, lupus, psoriasis, rheumatoid arthritis, sarcoidosis, Sjögren's syndrome, systemic sclerosis, and type 1 diabetes) is associated with risk of NHL. Methods Two-sample MR was performed using publicly available summary statistics from cohorts of European ancestry. For NHL and four NHL subtypes, we used data from UK Biobank, Kaiser Permanente cohorts, and FinnGen studies. Results Negative associations between type 1 diabetes and sarcoidosis and the risk of NHL were observed (odds ratio [OR] 0.95, 95% confidence interval [CI]: 0.92–0.98, p = 5 × 10−3, and OR 0.92, 95% CI: 0.85–0.99, p = 2.8 × 10−2, respectively). These findings were supported by the sensitivity analyses accounting for potential pleiotropy and weak instrument bias. No significant associations were found between the other eight autoimmune diseases and NHL risk. Conclusion These findings suggest that genetically predicted susceptibility to type 1 diabetes, and to some extent sarcoidosis, might reduce the risk of NHL. However, future studies with different datasets, approaches, and populations are warranted to further examine the potential associations between these autoimmune diseases and the risk of NHL.

• Rogne, Tormod; Wang, Rong; Wang, Pin; Deziel, Nicole C; Metayer, Catherine & Wiemels, Joseph L [Show all 9 contributors for this article] (2024). High ambient temperature in pregnancy and risk of childhood acute lymphoblastic leukaemia: an observational study. The Lancet Planetary Health. doi: 10.1016/S2542-5196(24)00121-9. Full text in Research Archive
• Ardissino, Maddalena; Morley, Alec; Slob, Eric; Schuermans, Art; Rayes, Bilal & Raisi-Estabragh, Zahra [Show all 11 contributors for this article] (2024). Birth weight influences cardiac structure, function, and disease risk: evidence of a causal association. European Heart Journal. ISSN 0195-668X. doi: 10.1093/eurheartj/ehad631. Full text in Research Archive
• Liyanarachi, Kristin Vardheim; Mohus, Randi Marie; Rogne, Tormod; Gustad, Lise Tuset; Åsvold, Bjørn Olav & Romundstad, Solfrid [Show all 9 contributors for this article] (2024). Chronic kidney disease and risk of bloodstream infections and sepsis: a 17-year follow-up of the population-based Trøndelag Health Study in Norway. Infection. ISSN 0300-8126. 52(5), p. 1983–1993. doi: 10.1007/s15010-024-02265-2. Full text in Research Archive Show summary

  Purpose: Bloodstream infections (BSI) and sepsis are important causes of hospitalization, loss of health, and death globally. Targetable risk factors need to be identified to improve prevention and treatment. In this study, we aimed to evaluate the association of chronic kidney disease (CKD) and risk of and mortality from BSI and sepsis in the general population during a 22-year period. Methods: We conducted a prospective cohort study among participants in the population-based Norwegian HUNT Study, where 68,438 participated. The median follow-up time was 17.4 years. The exposures were estimated glomerular filtration rate (eGFR) and albumin–creatinine ratio (ACR) in urine. The outcomes were hazard ratios (HR) of hospital admission or death due to BSI or sepsis. The associations were adjusted for age, sex, diabetes, obesity, systolic blood pressure, smoking status, and cardiovascular disease. Results: Participants with eGFR < 30 ml/min/1.732 had HR 3.35 for BSI (95% confidence intervals (CI) 2.12–5.3) and HR 2.94 for sepsis (95% CI 1.82–4.8) compared to normal eGFR (≥ 90 ml/min/1.732). HRs of death from BSI and sepsis were 4.2 (95% CI 1.71–10.4) and 4.1 (95% CI 1.88–8.9), respectively. Participants with severely increased albuminuria (ACR > 30 mg/mmol) had HR 3.60 for BSI (95% CI 2.30–5.6) and 3.14 for sepsis (95% CI 1.94–5.1) compared to normal albumin excretion (ACR < 3 mg/mmol). HRs of death were 2.67 (95% CI 0.82–8.7) and 2.16 (95% CI 0.78–6.0), respectively. Conclusion: In this large population-based cohort study, CKD was clearly associated with an increased risk of BSI and sepsis and related death.

• Nilsen, Sara Marie; Valand, Jonas; Rogne, Tormod; Asheim, Andreas; Yin, Weiyao & Metsälä, Johanna [Show all 13 contributors for this article] (2023). Gestational age at birth and hospitalisations for infections among individuals aged 0–50 years in Norway: a longitudinal, register-based, cohort study. EClinicalMedicine. 62, p. 1–13. doi: 10.1016/j.eclinm.2023.102108. Full text in Research Archive Show summary

  Background Preterm birth is associated with increased risk of childhood infections. Whether this risk persists into adulthood is unknown and limited information is available on risk patterns across the full range of gestational ages. Methods In this longitudinal, register-based, cohort study, we linked individual-level data on all individuals born in Norway (January 01, 1967–December 31, 2016) to nationwide hospital data (January 01, 2008–December 31, 2017). Gestational age was categorised as 23–27, 28–31, 32–33, 34–36, 37–38, 39–41, and 42–44 completed weeks. The analyses were stratified by age at follow-up: 0–11 months and 1–5, 6–14, 15–29, and 30–50 years. The primary outcome was hospitalisation due to any infectious disease, with major infectious disease groups as secondary outcomes. Adjusted hospitalisation rate ratios (RRs) for any infection and infectious disease groups were estimated using negative binomial regression. Models were adjusted for year of birth, maternal age at birth, parity, and sex, and included an offset parameter adjusted for person-time at risk. Findings Among 2,695,830 individuals with 313,940 hospitalisations for infections, we found a pattern of higher hospitalisation risk in lower gestational age groups, which was the strongest in childhood but still evident in adulthood. Comparing those born very preterm (28–31) and late preterm (34–36) to full-term (39–41 weeks), RRs (95% confidence interval) for hospitalisation for any infectious disease at ages 1–5 were 3.3 (3.0–3.7) and 1.7 (1.6–1.8), respectively. At 30–50 years, the corresponding estimates were 1.4 (1.2–1.7) and 1.2 (1.1–1.3). The patterns were similar for the infectious disease groups, including bacterial and viral infections, respiratory tract infections (RTIs), and infections not attributable to RTIs. Interpretation Increasing risk of hospitalisations for infections in lower gestational age groups was most prominent in children but still evident in adolescents and adults. Possible mechanisms and groups that could benefit from vaccinations and other prevention strategies should be investigated. Funding St. Olav's University Hospital and Norwegian University of Science and Technology, Norwegian Research Council, Liaison Committee for education, research and innovation in Central Norway, European Commission, Academy of Finland, Sigrid Jusélius Foundation, Foundation for Pediatric Research, and Signe and Ane Gyllenberg Foundation.

• Zhong, Charlie; Wang, Rong; Morimoto, Libby M.; Longcore, Travis; Franklin, Meredith & Rogne, Tormod [Show all 9 contributors for this article] (2023). Outdoor artificial light at night, air pollution, and risk of childhood acute lymphoblastic leukemia in the California Linkage Study of Early-Onset Cancers. Scientific Reports. 13(1). doi: 10.1038/s41598-022-23682-z. Full text in Research Archive Show summary

  Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children (age 0–14 years); however, the etiology remains incompletely understood. Several environmental exposures have been linked to risk of childhood ALL, including air pollution. Closely related to air pollution and human development is artificial light at night (ALAN), which is believed to disrupt circadian rhythm and impact health. We sought to evaluate outdoor ALAN and air pollution on risk of childhood ALL. The California Linkage Study of Early-Onset Cancers is a large population-based case–control in California that identifies and links cancer diagnoses from the California Cancer Registry to birth records. For each case, 50 controls with the same year of birth were obtained from birth records. A total of 2,782 ALL cases and 139,100 controls were identified during 2000–2015. ALAN was assessed with the New World Atlas of Artificial Night Sky Brightness and air pollution with an ensemble-based air pollution model of particulate matter smaller than 2.5 microns (PM2.5). After adjusting for known and suspected risk factors, the highest tertile of ALAN was associated with an increased risk of ALL in Hispanic children (odds ratio [OR] = 1.15, 95% confidence interval [CI] 1.01–1.32). There also appeared to be a borderline association between PM2.5 level and risk of ALL among non-Hispanic White children (OR per 10 µg/m3 = 1.24, 95% CI 0.98–1.56). We observed elevated risk of ALL in Hispanic children residing in areas of greater ALAN. Further work is needed to understand the role of ALAN and air pollution in the etiology of childhood ALL in different racial/ethnic groups.

• Grønseth, Stine; Rogne, Tormod; Heggelund, Lars; Åsvold, Bjørn Olav; Afset, Jan Egil & Damås, Jan Kristian (2023). Role of fungal burden in risk stratification of HIV-negative patients with Pneumocystis pneumonia: A 12-year, retrospective, observational, multicenter cohort. International Journal of Infectious Diseases. ISSN 1201-9712. 134, p. 177–186. doi: 10.1016/j.ijid.2023.06.013. Full text in Research Archive Show summary

  Objectives This study aimed to explore the role of fungal burden in risk stratification of patients without HIV-negative patients with Pneumocystis pneumonia (PCP). Methods This was a retrospective analysis of the characteristics associated with 30-day mortality in patients who were positive for P. jirovecii using polymerase chain reaction in bronchoalveolar lavage fluid between 2006 and 2017 in a multicenter cohort from Central Norway. The fungal burden was indicated by the cycle threshold (CT) values from semiquantitative real-time polymerase chain reaction targeting the β-tubulin gene. Results We included 170 patients with proven or probable PCP. The all-cause 30-day mortality was 18.2%. After adjusting for host characteristics and premorbid corticosteroid use, a higher fungal burden was associated with a higher risk of dying: adjusted odds ratio 1.42 (95% confidence interval 0.48-4.25) for a CT value 31-36, increasing to odds ratio 5.43 (95% confidence interval 1.48-19.9) for a CT value ≤30 compared with patients with a CT value ≥37. The Charlson comorbidity index (CCI) improved the risk stratification: patients with a CT value ≥37 and CCI ≤2 had a 9% mortality risk compared with 70% among those with a CT value ≤30 and CCI ≥6. Comorbid cardiovascular disease, solid tumors, immunological disorders, premorbid corticosteroids, hypoxemia, abnormal leukocyte counts, low serum albumin, and C-reactive protein ≥100 were also independently associated with 30-day mortality. The sensitivity analyses did not suggest selection bias. Conclusion Fungal burden may improve the risk stratification of patients without HIV-negative patients with PCP.

• Flatby, Helene Marie; Ravi, Anuradha; Damås, Jan Kristian; Solligård, Erik & Rogne, Tormod (2023). Circulating levels of micronutrients and risk of infections: a Mendelian randomization study. BMC Medicine. 21:84, p. 1–11. doi: 10.1186/s12916-023-02780-3. Full text in Research Archive Show summary

  Background Micronutrients play an essential role at every stage of the immune response, and deficiencies can therefore lead to increased susceptibility to infections. Previous observational studies and randomized controlled trials of micronutrients and infections are limited. We performed Mendelian randomization (MR) analyses to evaluate the effect of blood levels of eight micronutrients (copper, iron, selenium, zinc, beta-carotene, vitamin B12, vitamin C, and vitamin D) on the risk of three infections (gastrointestinal infections, pneumonia, and urinary tract infections). Methods Two-sample MR was conducted using publicly available summary statistics from independent cohorts of European ancestry. For the three infections, we used data from UK Biobank and FinnGen. Inverse variance-weighted MR analyses were performed, together with a range of sensitivity analyses. The threshold for statistical significance was set at P < 2.08E−03. Results We found a significant association between circulating levels of copper and risk of gastrointestinal infections, where a one standard deviation increase in blood levels of copper was associated with an odds ratio of gastrointestinal infections of 0.91 (95% confidence interval 0.87 to 0.97, P = 1.38E−03). This finding was robust in extensive sensitivity analyses. There was no clear association between the other micronutrients and the risk of infection. Conclusions Our results strongly support a role of copper in the susceptibility to gastrointestinal infections.

• Thorkildsen, Marianne Thorkildsen; Gustad, Lise Tuset; Mohus, Randi Marie; Burgess, Stephen; Nilsen, Tom Ivar Lund & Damås, Jan Kristian [Show all 7 contributors for this article] (2023). Association of Genetically Predicted Insomnia with Risk of Sepsis: A Mendelian Randomization Study. JAMA psychiatry. ISSN 2168-6238. 80(10), p. 1061–1065. doi: 10.1001/jamapsychiatry.2023.2717. Full text in Research Archive Show summary

  Importance Insomnia has been associated with altered inflammatory response as well as increased risk of infections and sepsis in observational studies. However, these studies are prone to bias, such as residual confounding. To further understand the potential causal association between insomnia and sepsis risk, a 2-sample Mendelian randomization (MR) approach should be explored. Objective To evaluate whether genetically predicted insomnia is associated with risk of sepsis. Design, Setting, and Participants Two-sample MR was performed to estimate the association between genetically predicted insomnia and sepsis risk. Data were obtained from a genome-wide association study identifying 555 independent genetic variants (R2 < 0.01) strongly associated with insomnia (P < 5 × 10−8). Sensitivity analyses were conducted to address bias due to pleiotropy and sample overlap, along with mediation analyses and sex-stratified analyses. The insomnia data set included 2.4 million individuals of European ancestry from the UK Biobank and 23andMe. For sepsis, 462 918 individuals of European ancestry from the UK Biobank were included. Data were extracted between February and December 2022 and analyzed between March 2022 and March 2023. Exposure Genetically predicted insomnia. Main Outcome and Measure Sepsis. Results There were 593 724 individuals with insomnia and 10 154 cases of sepsis. A doubling in the population prevalence of genetically predicted insomnia was associated with an odds ratio of 1.37 (95% CI, 1.19-1.57; P = 7.6 × 10−6) for sepsis. Sensitivity analyses supported this observation. One-third of the association between genetically predicted insomnia and risk of sepsis was mediated through a combination of cardiometabolic risk factors for sepsis (body mass index, type 2 diabetes, smoking, or cardiovascular disease; overall proportion, 35.2%; 95% CI, 5.1-76.9). The association between insomnia and sepsis was more pronounced among women compared with men (women: odds ratio, 1.44; 95% CI, 1.24-1.68; men: OR, 1.10; 95% CI, 0.86-1.40). Conclusions and Relevance The concordance between these findings and previous observational studies supports that insomnia is potentially causally associated with the risk of sepsis. Thus, insomnia is a potential preventable risk factor of sepsis that should be further investigated, also in non-European populations.

• Ardissino, Maddalena; Slob, Eric A. W.; Carter, Paul; Rogne, Tormod; Girling, Joanna & Burgess, Stephen [Show all 7 contributors for this article] (2023). Sex-Specific Reproductive Factors Augment Cardiovascular Disease Risk in Women: A Mendelian Randomization Study. Journal of the American Heart Association (JAHA). 12(5). doi: 10.1161/JAHA.122.027933. Full text in Research Archive
• Hosier, Hillary; Lipkind, Heather S.; Rasheed, Humaira; DeWan, Andrew & Rogne, Tormod (2023). Dyslipidemia and Risk of Preeclampsia: A Multiancestry Mendelian Randomization Study. Hypertension. ISSN 0194-911X. 80(5), p. 1067–1076. doi: 10.1161/HYPERTENSIONAHA.122.20426. Full text in Research Archive Show summary

  Abstract Background: Preeclampsia is a leading cause of maternal morbidity, and dyslipidemia has been associated with preeclampsia in observational studies. We use Mendelian randomization analyses to estimate the association between lipid levels, their pharmacological targets, and the risk of preeclampsia in 4 ancestry groups. Methods: We extracted uncorrelated (R2<0.001) single-nucleotide polymorphisms strongly associated (P<5×10-8) with LDL-C (low-density lipoprotein cholesterol), HDL-C (high-density lipoprotein cholesterol), and triglycerides from genome-wide association studies of European, admixed African, Latino, and East Asian ancestry participants. Genetic associations with risk of preeclampsia were extracted from studies of the same ancestry groups. Inverse-variance weighted analyses were performed separately for each ancestry group before they were meta-analyzed. Sensitivity analyses were conducted to evaluate bias due to genetic pleiotropy, demography, and indirect genetic effects. Results: The meta-analysis across 4 ancestry groups included 1.5 million subjects with lipid measurements, 7425 subjects with preeclampsia, and 239 290 without preeclampsia. Increasing HDL-C was associated with reduced risk of preeclampsia (odds ratio, 0.84 [95% CI, 0.74–0.94]; P=0.004; per SD increase in HDL-C), which was consistent across sensitivity analyses. We also observed cholesteryl ester transfer protein inhibition—a drug target that increases HDL-C—may have a protective effect. We observed no consistent effect of LDL-C or triglycerides on the risk of preeclampsia. Conclusions: We observed a protective effect of elevated HDL-C on risk of preeclampsia. Our findings align with the lack of effect in trials of LDL-C modifying drugs but suggest that HDL-C may be a new target for screening and intervention.

• Lawler, Patrick R.; Manvelian, Garen; Coppi, Alida; Damask, Amy; Cantor, Michael N. & Ferreira, Manuel A. R. [Show all 40 contributors for this article] (2023). Pharmacologic and Genetic Downregulation of Proprotein Convertase Subtilisin/Kexin Type 9 and Survival from Sepsis. Critical Care Explorations. 5(11), p. 1–12. doi: 10.1097/CCE.0000000000000997. Full text in Research Archive Show summary

  OBJECTIVES: Treatments that prevent sepsis complications are needed. Circulating lipid and protein assemblies—lipoproteins play critical roles in clearing pathogens from the bloodstream. We investigated whether early inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) may accelerate bloodstream clearance of immunogenic bacterial lipids and improve sepsis outcomes. DESIGN: Genetic and clinical epidemiology, and experimental models. SETTING: Human genetics cohorts, secondary analysis of a phase 3 randomized clinical trial enrolling patients with cardiovascular disease (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]; NCT01663402), and experimental murine models of sepsis. PATIENTS OR SUBJECTS: Nine human cohorts with sepsis (total n = 12,514) were assessed for an association between sepsis mortality and PCSK9 loss-of-function (LOF) variants. Incident or fatal sepsis rates were evaluated among 18,884 participants in a post hoc analysis of ODYSSEY OUTCOMES. C57BI/6J mice were used in Pseudomonas aeruginosa and Staphylococcus aureus bacteremia sepsis models, and in lipopolysaccharide-induced animal models. INTERVENTIONS: Observational human cohort studies used genetic PCSK9 LOF variants as instrumental variables. ODYSSEY OUTCOMES participants were randomized to alirocumab or placebo. Mice were administered alirocumab, a PCSK9 inhibitor, at 5 mg/kg or 25 mg/kg subcutaneously, or isotype-matched control, 48 hours prior to the induction of bacterial sepsis. Mice did not receive other treatments for sepsis. MEASUREMENTS AND MAIN RESULTS: Across human cohort studies, the effect estimate for 28-day mortality after sepsis diagnosis associated with genetic PCSK9 LOF was odds ratio = 0.86 (95% CI, 0.67–1.10; p = 0.24). A significant association was present in antibiotic-treated patients. In ODYSSEY OUTCOMES, sepsis frequency and mortality were infrequent and did not significantly differ by group, although both were numerically lower with alirocumab vs. placebo (relative risk of death from sepsis for alirocumab vs. placebo, 0.62; 95% CI, 0.32–1.20; p = 0.15). Mice treated with alirocumab had lower endotoxin levels and improved survival. CONCLUSIONS: PCSK9 inhibition may improve clinical outcomes in sepsis in preventive, pretreatment settings.

• Rogne, Tormod; Burgess, Stephen & Gill, Dipender (2022). Systemic iron status and maternal pregnancy complications: A Mendelian randomization study. International Journal of Epidemiology. ISSN 0300-5771. 51(3), p. 1024–1027. doi: 10.1093/ije/dyac037. Full text in Research Archive
• Camba, Alvaro Hernaez; Wootton, Robyn E; Page, Christian Magnus; Skåra, Karoline Hansen; Fraser, Abigail & Rogne, Tormod [Show all 12 contributors for this article] (2022). Smoking and infertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study. Fertility and Sterility. ISSN 0015-0282. 118(1), p. 180–190. doi: 10.1016/j.fertnstert.2022.04.001. Full text in Research Archive Show summary

  Objective: To investigate the association between smoking and infertility. Design: Prospective study. Setting: Nationwide cohort. Patients: 28,606 women and 27,096 men with questionnaire and genotype information from the Norwegian Mother, Father, and Child Cohort Study. Intervention: Self-reported information on smoking (having ever smoked [both sexes], age at initiation [women only], cessation [women only], and cigarettes/week in current smokers [both sexes]) was gathered. Genetically predetermined levels or likelihood of presenting these traits were estimated for Mendelian randomization. Main outcome: measure Infertility (time-to-pregnancy ≥12 months). Results: Having ever smoked was unrelated to infertility in women or men. Higher smoking intensity in women was associated with greater infertility odds (+1 standard deviation [SD, 48 cigarettes/week]: odds ratio [OR]crude, 1.19; 95% confidence interval [CI] 1.11–1.28; ORadjusted 1.12; 95% CI, 1.03–1.21), also after adjusting for the partner’s tobacco use. Later smoking initiation (+1 SD [3.2 years]: ORcrude, 0.94; 95% CI, 0.88–0.99; ORadjusted 0.89; 95% CI, 0.84–0.95) and smoking cessation (vs. not quitting: ORcrude, 0.83; 95% CI, 0.75–0.91; ORadjusted, 0.83; 95% CI, 0.75–0.93) were linked to decreased infertility in women. Nevertheless, Mendelian randomization results were not directionally consistent for smoking intensity and cessation and were estimated imprecisely in the 2-sample approach. In men, greater smoking intensity was not robustly associated with infertility in multivariable regression and Mendelian randomization. Conclusions: We did not find robust evidence of an effect of smoking on infertility. This may be due to a true lack of effect, weak genetic instruments, or other kinds of confounding.

• Liyanarachi, Kristin Vardheim; Solligård, Erik; Mohus, Randi Marie; Åsvold, Bjørn Olav; Rogne, Tormod & Damås, Jan Kristian (2022). Incidence, recurring admissions and mortality of severe bacterial infections and sepsis over a 22-year period in the population-based HUNT study. PLOS ONE. 17(7), p. 1–13. doi: 10.1371/journal.pone.0271263. Full text in Research Archive Show summary

  Purpose Severe bacterial infections are important causes of hospitalization and loss of health worldwide. In this study we aim to characterize the total burden, recurrence and severity of bacterial infections in the general population during a 22-year period. Methods We investigated hospitalizations due to bacterial infection from eight different foci in the prospective population-based Trøndelag Health Study (the HUNT Study), where all inhabitants aged ≥ 20 in a Norwegian county were invited to participate. Enrollment was between 1995 and 1997, and between 2006 and 2008, and follow-up ended in February 2017. All hospitalizations, positive blood cultures, emigrations and deaths in the follow-up period were captured through registry linkage. Results A total of 79,393 (69.5% and 54.1% of the invited population) people were included, of which 42,237 (53%) were women and mean age was 48.5 years. There were 37,298 hospitalizations due to infection, affecting 15,496 (22% of all included) individuals. The median time of follow-up was 20 years (25th percentile 9.5–75th percentile 20.8). Pneumonia and urinary tract infections were the two dominating foci with incidence rates of 639 and 550 per 100,000 per year, respectively, and with increasing incidence with age. The proportion of recurring admissions ranged from 10.0% (central nervous system) to 30.0% (pneumonia), whilst the proportion with a positive blood culture ranged from 4.7% (skin- and soft tissue infection) to 40.9% (central nervous system). The 30-day mortality varied between 3.2% (skin- and soft tissue infection) and 20.8% (endocarditis). Conclusions In this population-based cohort, we observed a great variation in the incidence, positive blood culture rate, recurrence and mortality between common infectious diseases. These results may help guide policy to reduce the infectious disease burden in the population.

• Thorkildsen, Marianne Thorkildsen; Laugsand, Lars Erik; Nilsen, Tom Ivar Lund; Mohus, Randi Marie; Høvik, Lise Husby & Rogne, Tormod [Show all 9 contributors for this article] (2022). Insomnia symptoms and risk of bloodstream infections: prospective data from the prospective population-based Nord-Trøndelag Health Study (HUNT), Norway. Journal of Sleep Research. ISSN 0962-1105. doi: 10.1111/jsr.13696. Full text in Research Archive
• Rogne, Tormod; Liew, Zeyan; Camba, Alvaro Hernaez; Brumpton, Ben Michael & Magnus, Maria Christine (2022). Modifiable risk factors for ectopic pregnancy: a Mendelian randomization study. American Journal of Obstetrics and Gynecology. ISSN 0002-9378. 227(2), p. 339–341. doi: 10.1016/j.ajog.2022.03.063. Full text in Research Archive
• Kousathanas, Athanasios; Pairo-Castineira, Erola; Rawlik, Konrad; Stuckey, Alex; Odhams, Christopher A. & Walker, Susan [Show all 824 contributors for this article] (2022). Whole-genome sequencing reveals host factors underlying critical COVID-19. Nature. ISSN 0028-0836. 607(7917), p. 97–103. doi: 10.1038/s41586-022-04576-6. Full text in Research Archive
• Mohus, Randi Marie; Gustad, Lise Tuset; Furberg, Anne-Sofie; Moen, Martine Kjølberg; Liyanarachi, Kristin Vardheim & Askim, Åsa Susanne [Show all 14 contributors for this article] (2022). Explaining sex differences in risk of bloodstream infections using mediation analysis in the population-based HUNT study in Norway. Scientific Reports. 12(1). doi: 10.1038/s41598-022-12569-8. Full text in Research Archive Show summary

  Previous studies indicate sex differences in incidence and severity of bloodstream infections (BSI). We examined the effect of sex on risk of BSI, BSI mortality, and BSI caused by the most common infecting bacteria. Using causal mediation analyses, we assessed if this effect is mediated by health behaviours (smoking, alcohol consumption), education, cardiovascular risk factors (systolic blood pressure, non-HDL cholesterol, body mass index) and selected comorbidities (cardiovascular disease, chronic kidney disease, diabetes, cancer history and chronic lung disease). This prospective study included 64,040 participants (46.8% men) in the population-based HUNT2 Survey (1995−97) linked with hospital records in incident BSI. During median follow-up of 14.8 years, 1840 (2.9%) participants (51.3% men) experienced a BSI and 396 (0.6%) died (56.6% men). Men had 41% higher risk of first-time BSI (95% confidence interval (CI), 28−54%) than women. Together, health behaviours, education, cardiovascular risk factors and the selected comorbidities mediated 34% of the excess risk of BSI observed in men. The HR of BSI mortality was 1.87 (95%CI, 1.53−2.28), for BSI due to S. aureus 2.09 (1.28−2.54), S. pneumoniae 1.36 (1.05−1.76), and E. coli 0.97 (0.84−1.13) in men vs women. This population-based study shows that men have higher risk of BSI and BSI mortality than women. One-third of this effect was mediated by potential modifiable risk factors for incident BSI.

• Mohus, Randi Marie; Flatby, Helene Marie; Liyanarachi, Kristin Vardheim; DeWan, Andrew; Solligård, Erik & Damås, Jan Kristian [Show all 9 contributors for this article] (2022). Iron status and the risk of sepsis and severe COVID-19: a two-sample Mendelian randomization study. Scientific Reports. 12(1). doi: 10.1038/s41598-022-20679-6. Full text in Research Archive
• Malik, Rainer; Georgakis, Marios K.; Vujkovic, Marijana; Damrauer, Scott M.; Elliott, Paul & Karhunen, Ville [Show all 17 contributors for this article] (2021). Relationship between Blood Pressure and Incident Cardiovascular Disease: Linear and Nonlinear Mendelian Randomization Analyses. Hypertension. ISSN 0194-911X. p. 2004–2013. doi: 10.1161/HYPERTENSIONAHA.120.16534. Full text in Research Archive Show summary

  Observational studies exploring whether there is a nonlinear effect of blood pressure on cardiovascular disease (CVD) risk are hindered by confounding. This limitation can be overcome by leveraging randomly allocated genetic variants in nonlinear Mendelian randomization analyses. Based on their association with blood pressure traits in a genome-wide association study of 299 024 European ancestry individuals, we selected 253 genetic variants to proxy the effect of modifying systolic and diastolic blood pressure. Considering the outcomes of incident coronary artery disease, stroke and the combined outcome of CVD, linear and nonlinear Mendelian randomization analyses were performed on 255 714 European ancestry participants without a history of CVD or antihypertensive medication use. There was no evidence favoring nonlinear relationships of genetically proxied systolic and diastolic blood pressure with the cardiovascular outcomes over linear relationships. For every 10-mm Hg increase in genetically proxied systolic blood pressure, risk of incident CVD increased by 49% (hazard ratio, 1.49 [95% CI, 1.38–1.61]), with similar estimates obtained for coronary artery disease (hazard ratio, 1.50 [95% CI, 1.38–1.63]) and stroke (hazard ratio, 1.44 [95% CI, 1.22–1.70]). Genetically proxied blood pressure had a similar relationship with CVD in men and women. These findings provide evidence to support that even for individuals who do not have elevated blood pressure, public health interventions achieving persistent blood pressure reduction will be of considerable benefit in the primary prevention of CVD.

• Camba, Alvaro Hernaez; Rogne, Tormod; Skåra, Karoline Hansen; Håberg, Siri Eldevik; Page, Christian Magnus & Fraser, Abigail [Show all 9 contributors for this article] (2021). Body mass index and subfertility: multivariable regression and Mendelian randomization analyses in the Norwegian Mother, Father and Child Cohort Study. Human Reproduction. ISSN 0268-1161. 36(12), p. 3141–3151. doi: 10.1093/humrep/deab224. Full text in Research Archive Show summary

  STUDY QUESTION What is the association between BMI and subfertility? SUMMARY ANSWER We observed a J-shaped relationship between BMI and subfertility in both sexes, when using both a standard multivariable regression and Mendelian randomization (MR) analysis. WHAT IS KNOWN ALREADY High BMI in both women and men is associated with subfertility in observational studies and this relationship is further substantiated by a few small randomized controlled trials of weight reduction and success of assisted reproduction. Women with low BMI also have lower conception rates with assisted reproduction technologies. STUDY DESIGN, SIZE, DURATION Cohort study (the Norwegian Mother, Father and Child Cohort Study), 28 341 women and 26 252 men, recruited from all over Norway between 1999 and 2008. PARTICIPANTS/MATERIALS, SETTING, METHODS Women (average age 30, average BMI 23.1 kg/m2) and men (average age 33, average BMI 25.5 kg/m2) had available genotype data and provided self-reported information on time-to-pregnancy and BMI. A total of 10% of couples were subfertile (time-to-pregnancy ≥12 months). MAIN RESULTS AND THE ROLE OF CHANCE Our findings support a J-shaped association between BMI and subfertility in both sexes using multivariable logistic regression models. Non-linear MR validated this relationship. A 1 kg/m2 greater genetically predicted BMI was linked to 18% greater odds of subfertility (95% CI 5% to 31%) in obese women (≥30.0 kg/m2) and 15% lower odds of subfertility (−24% to −2%) in women with BMI <20.0 kg/m2. A 1 kg/m2 higher genetically predicted BMI was linked to 26% greater odds of subfertility (8–48%) among obese men. Low genetically predicted BMI values were also related to greater subfertility risk in men at the lower end of the BMI distribution. A genetically predicted BMI of 23 and 25 kg/m2 was linked to the lowest subfertility risk in women and men, respectively. LIMITATIONS, REASONS FOR CAUTION The main limitations of our study were that we did not know whether the subfertility was driven by the women, men or both; the exclusive consideration of individuals of northern European ancestry; and the limited amount of participants with obesity or BMI values <20.0 kg/m2. WIDER IMPLICATIONS OF THE FINDINGS Our results support a causal effect of obesity on subfertility in women and men. Our findings also expand the current evidence by indicating that individuals with BMI values <20 kg/m2 may have an increased risk of subfertility. These results suggest that BMI values between 20 and 25 kg/m2 are optimal for a minimal risk of subfertility. STUDY FUNDING/COMPETING INTEREST(S) The MoBa Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Norwegian Ministry of Education and Research. This project received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreement No 947684). It was also partly supported by the Research Council of Norway through its Centres of Excellence funding scheme, project number 262700. Open Access funding was provided by the Folkehelseinstituttet/Norwegian Institute of Public Health. D.A.L. is a UK National Institute for Health Research Senior Investigator (NF-SI-0611-10196) and is supported by the US National Institutes of Health (R01 DK10324) and a European Research Council Advanced Grant (DevelopObese; 669545). The funders had no role in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. D.A.L. receives (or has received in the last 10 years) research support from National and International government and charitable bodies, Roche Diagnostics and Medtronic for research unrelated to the current work. The rest of the authors declare that no competing interests exist. TRIAL REGISTRATION NUMBER N/A.

• Rogne, Tormod; Liyanarachi, Kristin Vardheim; Rasheed, Humaira; Thomas, Laurent; Flatby, Helene Marie & Stenvik, Jørgen [Show all 16 contributors for this article] (2021). GWAS Identifies LINC01184/SLC12A2 as a Risk Locus for Skin and Soft Tissue Infections. Journal of Investigative Dermatology. ISSN 0022-202X. 141(8), p. 2083–2086.e8. doi: 10.1016/j.jid.2021.01.020. Full text in Research Archive
• Grønseth, Stine; Rogne, Tormod; Hannula, Raisa; Åsvold, Bjørn Olav; Afset, Jan Egil & Damås, Jan Kristian (2021). Semiquantitative Real-Time PCR to Distinguish Pneumocystis Pneumonia from Colonization in a Heterogeneous Population of HIV-Negative Immunocompromised Patients. Microbiology spectrum. 9(1), p. e0002621–e0002621. doi: 10.1128/Spectrum.00026-21. Full text in Research Archive Show summary

  Pneumocystis jirovecii is a threat to iatrogenically immunosuppressed individuals, a heterogeneous population at rapid growth. We assessed the ability of an in-house semiquantitative real-time PCR assay to discriminate Pneumocystis pneumonia (PCP) from colonization and identified risk factors for infection in these patients. Retrospectively, 242 PCR-positive patients were compared according to PCP status, including strata by immunosuppressive conditions, human immunodeficiency virus (HIV) infection excluded. Associations between host characteristics and cycle threshold (CT) values, semiquantitative real-time PCR correlates of fungal loads in lower respiratory tract specimens, were investigated. CT values differed significantly according to PCP status. Overall, a CT value of 36 allowed differentiation between PCP and colonization with sensitivity and specificity of 71.3% and 77.1%, respectively. A CT value of less than 31 confirmed PCP, whereas no CT value permitted exclusion. A considerable diversity was uncovered; solid organ transplant (SOT) recipients had significantly higher fungal loads than patients with hematological malignancies. In SOT recipients, a CT cutoff value of 36 resulted in sensitivity and specificity of 95.0% and 83.3%, respectively. In patients with hematological malignancies, a higher CT cutoff value of 37 improved sensitivity to 88.5% but reduced specificity to 66.7%. For other conditions, assay validity appeared inferior. Corticosteroid usage was an independent predictor of PCP in a multivariable analysis and was associated with higher fungal loads at PCP expression. Semiquantitative real-time PCR improves differentiation between PCP and colonization in immunocompromised HIV-negative individuals with acute respiratory syndromes. However, heterogeneity in disease evolution requires separate cutoff values across intrinsic and iatrogenic predisposition for predicting non-HIV PCP. IMPORTANCE Pneumocystis jirovecii is potentially life threatening to an increasing number of individuals with compromised immune systems. This microorganism can cause severe pneumonia in susceptible hosts, including patients with cancer and autoimmune diseases and people undergoing solid organ transplantation. Together, these patients constitute an ever-diverse population. In this paper, we demonstrate that the heterogeneity herein has important implications for how we diagnose and assess the risk of Pneumocystis pneumonia (PCP). Specifically, low loads of microorganisms are sufficient to cause infection in patients with blood cancer compared to those in solid organ recipients. With this new insight into host versus P. jirovecii biology, clinicians can manage patients at risk of PCP more accurately. As a result, we take a significant step toward offering precision medicine to a vulnerable patient population. One the one hand, these patients have propensity for adverse effects from antimicrobial treatment. On the other hand, this population is susceptible to life-threatening infections, including PCP.

• Flatby, Helene Marie; Rasheed, Humaira; Ravi, Anuradha; Thomas, Laurent; Liyanarachi, Kristin Vardheim & Afset, Jan Egil [Show all 15 contributors for this article] (2021). Risk of lower respiratory tract infections: a genome-wide association study with Mendelian randomization analysis in three independent European populations. Clinical Microbiology and Infection (CMI). ISSN 1198-743X. 28(5), p. 732.e1–732.e7. doi: 10.1016/j.cmi.2021.11.004. Full text in Research Archive Show summary

  Objective: Lower respiratory tract infections (LRTIs) are a leading cause of morbidity and mortality worldwide. Few studies have previously investigated the genetic susceptibility and potential risk factors for LRTI. Methods: We used data from UK Biobank, HUNT, and FinnGen, to conduct a genome-wide association study (GWAS). Cases were subjects hospitalized with LRTI, and controls were subjects with no such hospitalization. We conducted stratification and interaction analyses to evaluate if the genetic effect of LRTI differed by sex or smoking. Mendelian randomization [MR] analyses were conducted to identify the unconfounded relationship between cardiometabolic risk factors and LRTI. Results: A total of 25,320 cases and 575,294 controls were included. The 15q25.1 locus reached genome-wide significance in the meta-analysis (rs10519203: OR = 0.94, P = 3.87e-11). The protective effect of effect allele of rs10519203 was present among smokers (OR = 0.90 [95% CI = 0.87 - 0.92, P = 1.38e-15]) but not among never-smokers (OR = 1.01 [95% CI = 0.97 - 1.06, P = 5.20e-01]). In MR analyses, we found that increasing body mass index (OR = 1.31 [95% CI = 1.24 - 1.40, P = 3.78e-18]), lifetime smoking (OR = 2.83 [95% CI = 2.34 - 3.42, P = 6.56e-27]), and systolic blood pressure robustly increased the risk of LRTIs (OR = 1.11 [95% CI = 1.02 - 1.22, P = 1.48e-02]). Conclusion: A region in 15q25.1 was strongly associated with LRTI susceptibility. Reduction of the prevalence of smoking, overweight, obesity, and hypertension may reduce the disease burden of LRTIs. Keywords: body mass index, genome-wide association study, lowerrespiratory tract infection, mendelianrandomization, pneumonia, respiratory infection, smoking

• Grønseth, Stine; Rogne, Tormod; Hannula, Raisa; Åsvold, Bjørn Olav; Afset, Jan Egil & Damås, Jan Kristian (2021). Epidemiological and clinical characteristics of immunocompromised patients infected with Pneumocystis jirovecii in a twelve-year retrospective study from Norway. BMC Infectious Diseases. 21(1). doi: 10.1186/s12879-021-06144-1. Full text in Research Archive
• Rogne, Tormod; Damås, Jan Kristian; Flatby, Helene Marie; Åsvold, Bjørn Olav; DeWan, Andrew & Solligård, Erik (2021). The Role of FER rs4957796 in the Risk of Developing and Dying from a Bloodstream Infection: A 23-Year Follow-up of the Population-based Nord-Trøndelag Health Study. Clinical Infectious Diseases. ISSN 1058-4838. 73(2), p. 1–7. doi: 10.1093/cid/ciaa786. Full text in Research Archive
• Brown, Paul; Rogne, Tormod & Solligård, Erik (2020). The promise and pitfalls of composite endpoints in sepsis and COVID-19 clinical trials. Pharmaceutical statistics. ISSN 1539-1604. doi: 10.1002/pst.2070. Full text in Research Archive
• Rogne, Tormod; Solligård, Erik; Burgess, Stephen; Brumpton, Ben Michael; Paulsen, Julie & Pescott, Hallie [Show all 12 contributors for this article] (2020). Body mass index and risk of dying from a bloodstream infection: A Mendelian randomization study. PLoS Medicine. ISSN 1549-1277. 17(11). doi: 10.1371/journal.pmed.1003413. Full text in Research Archive
• Ponsford, Mark J; Gkatzionis, Apostolos; Walker, Venexia M; Grant, Andrew J; Wootton, Robyn E & Moore, Luke [Show all 21 contributors for this article] (2020). Cardiometabolic traits, sepsis and severe covid-19: a Mendelian randomization investigation. Circulation. ISSN 0009-7322. 142(18), p. 1791–1793. doi: 10.1161/CIRCULATIONAHA.120.050753. Full text in Research Archive
• Giri, Samita; Halvas-Svendsen, Tine; Rogne, Tormod; Shrestha, Sanu Krishna; Døllner, Henrik & Solligård, Erik [Show all 7 contributors for this article] (2020). Pediatric Patients in a Local Nepali Emergency Department: Presenting Complaints, Triage and Post-Discharge Mortality. Global Pediatric Health. 7. doi: 10.1177/2333794X20947926. Full text in Research Archive Show summary

  Background. In low-income countries, pediatric emergency care is largely underdeveloped although child mortality in emergency care is more than twice that of adults, and mortality after discharge is high. Aim. We aimed at describing characteristics, triage categories, and post-discharge mortality in a pediatric emergency population in Nepal. Methods. We prospectively assessed characteristics and triage categories of pediatric patients who entered the emergency department (ED) in a local hospital. Patient households were followed-up by telephone interviews at 90 days. Results. The majority of pediatric emergency patients presented with injuries and infections (~40% each). Girls attended ED less frequent than boys. High triage priority categories (orange and red) were strong indicators for intensive care need and for mortality after discharge. Conclusion. The study supports the use and development of a pediatric triage systems in a low-resource general ED setting. We identify a need for interventions that can reduce mortality after pediatric emergency care. Interventions to reduce pediatric emergency disease burden in this setting should emphasize prevention and effective treatment of infections and injuries.

• Rogne, Tormod; Damås, Jan Kristian; Solligård, Erik & DeWan, Andrew (2020). Genome-Wide Linkage Analysis of the Risk of Contracting a Bloodstream Infection in 47 Pedigrees Followed for 23 Years Assembled From a Population-based Cohort (the HUNT Study). Critical Care Medicine. ISSN 0090-3493. 48(11), p. 1580–1586. doi: 10.1097/CCM.0000000000004520. Full text in Research Archive
• Giri, Samita; Rogne, Tormod; Uleberg, Oddvar; Skovlund, Eva; Shrestha, Sanu Krishna & Koju, Rajendra [Show all 9 contributors for this article] (2019). Presenting complaints and mortality in a cohort of 22 000 adult emergency patients at a local hospital in Nepal. Journal of Global Health. ISSN 2047-2978. 9(2). doi: 10.7189/jogh.09.020403. Full text in Research Archive Show summary

  Background There is a need to develop sustainable emergency health care systems in low-resource settings, but data that analyses emergency health care needs in these settings are scarce. We aimed at assessing presenting complaints (PCs) and post-discharge mortality in a large emergency department population in Nepal. Methods Characteristics of adult patients who entered the emergency department (ED) in a hospital in Nepal were prospectively recorded in the local emergency registry from September 2013 until December 2016. To assess post-ED mortality, patient households were followed-up by telephone interviews at 90 days. Results In 21892 included adults, the major PC categories were injuries (29%), abdominal complaints (23%), and infections (16%). Median age was 40 years and sex distribution was balanced. Among 3793 patients followed at 90 days, 8% had died. For respiratory and cardiovascular PCs, 90-day mortality were 25% and 23%. The highest mortality was in individuals with known chronic lung disease, in this group 32% had died by 90 days of ED discharge, regardless of PC. In women, illiteracy compared to literacy (adjusted odds ratio (aOR) = 7.0, 95% confidence interval (CI) = 2.1-23.6) and being both exposed to tobacco-smoking and traditional cooking stove compared to no smoke (aOR = 2.8, 95% CI = 1.6-4.9) were associated with mortality. The mortality was much higher among family-initiated discharged patients (17%, aOR = 5.4, 95% CI = 3.3-8.9) compared to doctor-initiated discharged (3%). Conclusions Our report suggests that nearly one in ten patients seeking emergency health care died within 90 days. This finding is alarming and novel. Post-discharge studies need to be replicated and appropriate follow-up programs in low-resource settings where primary health care is underdeveloped are urgently needed.

• Giri, Samita; Risnes, Kari Ravndal; Uleberg, Oddvar; Rogne, Tormod; Shrestha, Sanu Krishna & Nygaard, Øystein Petter [Show all 8 contributors for this article] (2018). Impact of 2015 Earthquakes on a local hospital in Nepal: A Prospective Hospital-based Study. PLOS ONE. 13(2), p. 1–16. doi: 10.1371/journal.pone.0192076. Full text in Research Archive Show summary

  Introduction Natural disasters pose a great challenge to the health systems and individual health facilities. In low-resource settings, disaster preparedness systems are often limited and not been well described. Two devastating earthquakes hit Nepal within a 17-days period in 2015. This study aims to describe the burden and distribution of emergency cases to a local hospital. Methods This is a prospective observational study of patients presenting to a local hospital for a period of 21 days following the earthquake on April 25, 2015. Demographic and clinical information was prospectively registered for all patients in the systematic emergency registry. Systematic telephone interviews were conducted in a random sample of the patients 90 days after admission to the hospital. Results A total of 2,003 emergency patients were registered during the period. The average daily number of emergency patients during the first five days was almost five times higher (n = 150) than the pre-incident daily average (n = 35). The majority of injuries were fractures (58%), 348 (56%) in the lower extremities. A total of 345 surgical procedures were performed and the hospital treated 111 patients with severe injuries related to the earthquake (compartment syndrome, crush injury, and internal injury). Among those with follow-up interviews, over 90% reported that they had been severely affected by the earthquakes; complete house damage, living in temporary shelter, or loss of close family member. Conclusion The hospital experienced a very high caseload during the first days, and the majority of patients needed orthopaedic services. The proportion of severely injured and in-hospital deaths were relatively low, probably indicating that the most severely injured did not reach the hospital in time. The experiences underline the need for robust and easily available local health services that can respond to disasters.

• Rogne, Tormod; Nordseth, Trond; Marhaug, Gudmund; Berg, Einar Marcus; Tromsdal, Arve & Sæther, Ola Dalsegg [Show all 10 contributors for this article] (2018). Rate of avoidable deaths in a Norwegian hospital trust as judged by retrospective chart review. BMJ Quality and Safety. ISSN 2044-5415. 28(1), p. 49–55. doi: 10.1136/bmjqs-2018-008053. Full text in Research Archive
• Larose, Tricia L; Turner, Steve W; Hutcheon, Jennifer A; Rogne, Tormod; Riphagen, Ingrid Ingeborg & Martinussen, Marit [Show all 7 contributors for this article] (2017). Longitudinal ultrasound measures of fetal growth and offspring outcomes. Current Epidemiology Reports. ISSN 2196-2995. 4(2), p. 98–105. doi: 10.1007/s40471-017-0103-2. Full text in Research Archive Show summary

  Purpose of Review In this narrative review, we outline recent evidence relating longitudinal ultrasound (US) measurements to offspring outcomes in the perinatal period and in childhood, with an emphasis on the methodological approaches for describing fetal growth. Recent Findings The utility of longitudinal ultrasonography (US) to measure fetal growth and determine fetal trajectories is valued in both clinical and research environments. Evidence shows that repeated measures of US throughout pregnancy are useful for distinguishing between a growth-restricted and constitutionally small fetus, the former burdened by adverse clinical outcomes. Fetal growth restriction and small for gestational age are not interchangeable terms, although both can exist in the same individual. Summary The application of longitudinal US may have predictive value when determining longer-term health and disease outcomes in offspring born growth-restricted. However, it is important to remember that associations between fetal growth restriction and increased risk for non-communicable diseases are likely modified by postnatal growth.

• Rogne, Tormod; Tielemans, Myrte J.; Chong, Mary Foong-Fong; Yajnik, Chittaranjan S.; Krishnaveni, Ghattu V. & Poston, Lucilla [Show all 24 contributors for this article] (2017). Associations of maternal vitamin B12 concentration in pregnancy with the risks of preterm birth and low birth weight: a systematic review and meta-analysis of individual participant data. American Journal of Epidemiology. ISSN 0002-9262. 185(3), p. 212–223. doi: 10.1093/aje/kww212. Full text in Research Archive Show summary

  Vitamin B12 (hereafter referred to as B12) deficiency in pregnancy is prevalent and has been associated with both lower birth weight (birth weight <2,500 g) and preterm birth (length of gestation <37 weeks). Nevertheless, current evidence is contradictory. We performed a systematic review and a meta-analysis of individual participant data to evaluate the associations of maternal serum or plasma B12 concentrations in pregnancy with offspring birth weight and length of gestation. Twenty-two eligible studies were identified (11,993 observations). Eighteen studies were included in the meta-analysis (11,216 observations). No linear association was observed between maternal B12 levels in pregnancy and birth weight, but B12 deficiency (<148 pmol/L) was associated with a higher risk of low birth weight in newborns (adjusted risk ratio = 1.15, 95% confidence interval (CI): 1.01, 1.31). There was a linear association between maternal levels of B12 and preterm birth (per each 1-standard-deviation increase in B12, adjusted risk ratio = 0.89, 95% CI: 0.82, 0.97). Accordingly, B12 deficiency was associated with a higher risk of preterm birth (adjusted risk ratio = 1.21, 95% CI: 0.99, 1.49). This finding supports the need for randomized controlled trials of vitamin B12 supplementation in pregnancy.

• Rogne, Tormod; Engstrøm, Andreas Aass; Jacobsen, Geir Wenberg; Skranes, Jon Sverre; Østgård, Heidi Furre & Martinussen, Marit (2015). Fetal growth, cognitive function, and brain volumes in childhood and adolescence. Obstetrics and Gynecology. ISSN 0029-7844. 125(3), p. 673–682. doi: 10.1097/AOG.0000000000000694. Full text in Research Archive
• Rogne, Tormod & Jacobsen, Geir Wenberg (2014). Association between low blood glucose increase during glucose tolerance tests in pregnancy and impaired fetal growth. Acta Obstetricia et Gynecologica Scandinavica. ISSN 0001-6349. 93(11), p. 1160–1169. doi: 10.1111/aogs.12365. Full text in Research Archive

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• Dietrichs, Erik Sveberg; Rogne, Tormod; Solberg, Carl Tollef & Nordengen, Kaja (2026). Norge trenger flere forskere, da må vi rekruttere tidligere. Full text in Research Archive Show summary

  KRONIKK: For første gang på 55 år er det nedgang i antall forskere. Ved norske universiteter og høyskoler var det 770 færre forskere i 2024 sammenlignet med 2023.

• Chock, Eugenia Y.; Rice, Tyler; Zhao, Tingting; Basile, Bridget & Rogne, Tormod (2025). Applying the small vulnerable newborns classification in the US context. International Journal of Gynecology & Obstetrics. ISSN 0020-7292. 172(2), p. 1261–1263. doi: 10.1002/ijgo.70479. Full text in Research Archive
• Thorkildsen, Marianne Thorkildsen; Flatby, Helene Marie; Åsvold, Bjørn Olav; Mohus, Randi Marie; Ellervik, Christina & Teumer, Alexander [Show all 11 contributors for this article] (2025). Thyroid Function and Risk of Sepsis: Triangulation from Prospective Observational and Mendelian Randomization Analyses. Dr.med. - Norwegian Journal of Epidemiology. Suppl.. 33(1). doi: https:/www.ntnu.no/ojs/index.php/norepid. Full text in Research Archive Show summary

  Introduction: Thyroid hormones modulate cells in the immune system; however, the risk associated with thyroid function and risk of infectious diseases remains unclear. This study triangulates observational and Mendelian randomization (MR) analyses to investigate thyroid-stimulating hormone (TSH) levels and risk of sepsis. Aims: To investigate the association between thyroid function and risk of sepsis. Methods: In observational analysis of 45,364 individuals aged >18 years from the Trøndelag Health Study (HUNT2 and HUNT3), we used Cox regression analyses to estimate the association between TSH levels at HUNT participation with risk of hospitalization with sepsis adjusted for sex, marital status, education level, smoking and body mass index. Two-sample MR analyses were performed using summary statistics of genetically predicted TSH levels from the ThyroidOmics Consortium (n= 271,040) with genetic liability to sepsis using UK Biobank (n=10,154 sepsis cases and 462,918 controls). Secondary analyses were conducted to explore associations between other thyroid function measures and risk of sepsis, or between TSH levels and risk of lower respiratory tract infections and upper urinary tract infections – two of the most common causes of sepsis. Results: In the observational analysis, we found little evidence that TSH levels increased risk of sepsis (hazard ratio 0.98 [95% CI 0.93–1.04] per mU/L unit increase). Participants with TSH levels < 0.5 mU/L had increased risk of sepsis (HR 1.50, 95% CI 1.19–1.90), compared with the reference range (0.5–1.4 mU/L). In the MR analysis we found no evidence of a causal relationship between genetically-predicted TSH levels and risk of sepsis (odds ratio 1.04 [95% CI 0.98–1.10] per standard deviation unit increase), nor between low levels of TSH and sepsis (odds ratio 0.98, 95% CI 0.94–1.10). Secondary analyses generally supported that there was no clear link between thyroid function and risk of sepsis or other severe infections. Conclusion: While observational data suggested higher sepsis risk with low TSH, genetic evidence points to that this may reflect confounding by comorbidities. Triangulating observational and genetic methods, we did not observe a robust association between thyroid function measures and the risk of severe infectious diseases.

• Myklebust, Åsne; Døllner, Henrik; Pape, Kristine; Rogne, Tormod & Risnes, Kari (2024). Early-life lower respiratory tract infection (LRTI) and risk of school-age asthma- a population-based cohort study. Full text in Research Archive
• Nilsen, Sara Marie; Valand, Jonas; Rogne, Tormod; Asheim, Andreas; Weiyao, Yin & Metsälä, Johanna [Show all 13 contributors for this article] (2023). Elevated infection risk in lower gestational age groups - most prominent in children but still evident in adults. Full text in Research Archive
• Pathak, Gita A.; Karjalainen, Juha; Stevens, Christine; Neale, Benjamin M.; Daly, Mark & Ganna, Andrea [Show all 833 contributors for this article] (2022). A first update on mapping the human genetic architecture of COVID-19. Nature. ISSN 0028-0836. 608(7921), p. E1–E10. doi: 10.1038/s41586-022-04826-7. Full text in Research Archive
• Mohus, Randi Marie; Gustad, Lise Tuset; Furberg, Anne-Sofie; Moen, Martine Kjølberg; Liyanarachi, Kristin Vardheim & Askim, Åsa Susanne [Show all 14 contributors for this article] (2021). Sex differences in incidence of bloodstream infections and the mediating role of known risk factors. Results from the population-based HUNT study in Norway. Norsk Epidemiologi, Supplement. ISSN 0803-4206. Full text in Research Archive
• Videm, Vibeke & Rogne, Tormod (2017). For lite mat fra dyr kan øke gravides risiko for tidlig fødsel. [Internet]. Gemini. Full text in Research Archive
• Gustad, Lise Tuset; Thorkildsen, Marianne Thorkildsen; Mohus, Randi Marie; Rogne, Tormod & Åsvold, Bjørn Olav (2025). Thyroid Function and Insomnia as Risk Factors for Bloodstream Infections and Sepsis. Norges teknisk-naturvitenskapelige universitet. ISSN 9788232686797. Full text in Research Archive

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