Obsessive-compulsive disorder (OCD) is a heritable neuropsychiatric phenotype with complex etiology. Like many others, this neuropsychiatric phenotype exhibits differences in clinical features between males and females, however, no study to date has characterized the genome-wide sex-specific genetic basis of these traits. The genome-wide association studies published to date using large OCD cohorts to uncover genetic contributors to disease, have not identified genome-wide significant genetic associations. This could be due to lack of sufficient power to detect small genetic effects and to characterize effects of rare genetic variants, consistent with the observation that OCD exhibits a highly polygenic architecture . Additionally, given the differences in the clinical features of OCD (earlier age of onset in males) between sexes, it is reasonable to hypothesize that genetic liability is influenced by sex-specific factors.
I am leading a project that explores the genetic role of sex in OCD. The aims of the project are to (1) investigate the genetic architectural differences driving sexually dimorphic features of OCD, and (2) to develop a novel analytic framework for sex-stratified genomic analysis. In the long-term the outcomes of this work will enable a deeper understanding of how genetic variants may regulate the biological processes influencing sex-biased phenotype development and provide insight into identifying sex-specific clinically targetable pathways.