Shared genetic loci and causal relations between schizophrenia and obsessive-compulsive disorder

Abstract

Based on the clinical overlap between schizophrenia (SCZ) and obsessive-compulsive disorder (OCD), both disorders may share neurobiological substrates. In this study, we first analyzed recent large genome-wide associations studies (GWAS) on SCZ (n = 53,386, Psychiatric Genomics Consortium Wave 3) and OCD (n = 2688, the International Obsessive-Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and the OCD Collaborative Genetics Association Study (OCGAS)) using a conjunctional false discovery rate (FDR) approach to evaluate overlap in common genetic variants of European descent. Using a variety of biological resources, we functionally characterized the identified genomic loci. Then we used two-sample Mendelian randomization (MR) to estimate the bidirectional causal association between SCZ and OCD. Results showed that there is a positive genetic correlation between SCZ and OCD (rg = 0.36, P = 0.02). We identified that one genetic locus (lead SNP rs5757717 in an intergenic region at CACNA1I) was jointly associated with SCZ and OCD (conjFDR = 2.12 × 10−2). Mendelian randomization results showed that variants associated with increased risk for SCZ also increased the risk of OCD. This study broadens our understanding of the genetic architectures underpinning SCZ and OCD and suggests that the same molecular genetic processes may be responsible for shared pathophysiological and clinical characteristics between the two disorders.