Click here to stream the trial lecture
Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Olli Kampman, Umeå University/University of Turku, Sweden/Finland
- Second opponent: Professor Jørgen G. Bramness, UiT The Arctic University of Norway
- Third member and chair of the evaluation committee: Associate Professor Linda Elise Couëssurel Wüsthoff, University of Oslo
Chair of the Defence
Associate Professor Paulina Due-Tønnessen, University of Oslo
Principal Supervisor
Associate Professor Olav Bjerkehagen Smeland, University of Oslo
Summary
This thesis in psychiatric genetics addresses the genetic architecture of opioid use disorder (OUD) and its overlap with related traits. OUD is a disorder that affects millions of people worldwide and is associated with nearly 100,000 deaths annually, yet its genetic basis remains incompletely understood. The thesis asks whether OUD shares genetic architecture with severe mental disorders (schizophrenia, bipolar disorder, major depression), general cognitive ability, and other substance use disorders (alcohol and cannabis), including overlap not captured by genetic correlation.
Three studies analysed GWAS summary statistics pairwise, using linkage disequilibrium score regression and polygenic scores (Study I), the mixture model MiXeR, which estimates shared causal variants irrespective of effect direction (Studies II and III), and conditional/conjunctional false discovery rate analysis, which uses a better-powered trait to improve locus discovery and identify shared loci.
Study I identified 20 OUD loci, 14 novel, of which seven were shared with severe mental disorders, all with concordant effect direction. Study II showed that 94% of OUD risk variants are also associated with cognitive ability and identified a novel shared locus in SLC5A11. Study III found 23 loci shared between alcohol and cannabis use disorder and 11 between alcohol and opioid use disorder, and contributed 39, 10, and one novel locus for alcohol, cannabis, and opioid use disorder, respectively. Across studies, 64 OUD loci were identified, many novel. OUD was the least polygenic trait examined. Shared loci implicated neuronal communication and development, and regulation of gene activity.
The findings indicate considerable shared genetic architecture, supporting shared biology behind comorbidity. Limitations include sample overlap, predominantly European ancestry, and limited power for OUD-specific validation. The results may inform biologically grounded classification and treatment.
Additional information
Contact the research support staff.