Click here to stream the public defence
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Cathryn Lewis, King's College London, UK
- Second opponent: Professor Andreas Reif, Goethe University, Germany
- Third member and chair of the evaluation committee: Professor Thomas Clausen, University of Oslo
Chair of the Defence
Professor Erik Gunnar Jönsson, University of Oslo
Principal Supervisor
Professor Ole Andreassen, University of Oslo
Summary
Genetic predisposition to mental disorders, like schizophrenia, bipolar disorder, major depression, and ADHD, and related traits, such as personality, cognitive function, and migraine, is driven by many individual genetic variants (polygenicity), many of which are associated with multiple different traits (pleiotropy). Hundreds of risk-modifying regions of the genome have been discovered for these traits, but these “genetic loci” explain a fraction of the traits’ heritability. The full extent of the polygenicity and pleiotropy of mental disorders and related traits is therefore poorly understood. The aims of this thesis were to quantify and characterise the polygenicity and pleiotropy of mental disorders and related traits and to leverage pleiotropy to boost genetic discovery and improve genetic prediction.
Bespoke statistical genetics tools were applied to genome-wide association studies of schizophrenia, bipolar disorder, major depression, ADHD, personality traits, cognitive function, and migraine. Data were derived from international consortia and population-based samples.
Mental disorders were more polygenic than somatic traits, such as migraine. There was also variation in the polygenicity of mental disorders, with major depression three times more polygenic than ADHD. This may indicate differences in the heterogeneity and/or biological complexity of mental disorders. There was extensive pleiotropy across mental disorders and related traits, with most genetic variants associated with one mental disorder also associated with a second. Pleiotropy was leveraged to identify several novel genetic loci jointly associated with mental disorders and migraine and to improve genetic prediction of cognitive function and personality. These findings provide a more nuanced understanding of the genetic underpinnings of mental disorders, which can contribute to the discovery of novel biological mechanisms and improve genetic prediction and personalised treatment.
Additional information
Contact the research support staff.