Abstract
Background Obsessive-Compulsive Disorder (OCD), a heritable neurobehavioral disorder, demonstrates sexual dimorphism in age of onset and clinical presentation, suggesting a possible sex difference in genetic architecture. Here, we present the first genome-wide assessment of sex-specific genetic architecture of OCD on currently the largest OCD cohort available from the Psychiatric Genomics Consortium (total cases and controls N=9,870 after quality control, 1:1.4 male/female ratio). Methods First, we performed a sex-stratified meta-GWAS to identify specific autosomal and sex chromosome genetic variants differentially associated to OCD risk in each of the sexes. Second, we assessed whether the most heterogeneous OCD risk alleles and top (p Results There were no genome-wide significant associations in either sex. Sex heterogenous SNPs (including and excluding SNPs in the HLA region) were strongly enriched for immune expression quantitative trait loci (p Discussion We present the first genome-wide assessment of sex-specific genetic architecture of OCD. We identified minor sex differences in genetic architecture of OCD, and although the sex-stratified sample size is likely too small to identify variants with small effect, we have developed a robust analytic pipeline for sex-stratified genetic analysis which will be applied in the near future to OCD as larger cohorts become available. The pipeline will also be applied to additional phenotypes where a sex bias in genetic effects may influence trait variation. This will enable a deeper understanding of how genetic variants may regulate biological processes influencing sex-biased phenotypes.
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