Genome-wide Association Study of Pediatric Obsessive-Compulsive Traits: Shared Genetic Risk between Traits and Disorder

This study examined the genetic correlates of obsessive-compulsive (OC) traits and their shared genetic risks with obsessive-compulsive disorder (OCD). We conducted genome-wide association analyses on OC traits in 5018 unrelated Caucasian children and adolescents. Overall OC traits and trait dimensions (e.g., cleaning/contamination) were measured with the Toronto Obsessive-Compulsive scale (TOCS). One locus tagged by rs7856850 in an intron of (protein tyrosine phosphatase δ) was associated with OC traits at the genome-wide significance level (=2.48×10). A variant in was significantly associated with only the symmetry/ordering dimension (=3.2×10). We tested the role of central nervous system (CNS) and glutamate gene-sets using hypothesis-driven methods. A stratified False Discovery Rate found OC traits were associated with SNPs in three CNS genes: (=7.8×10), (=1.6×10) and (=1.9×10). The combined effect of neither the CNS development nor the glutamate gene-set were associated with OC traits using the competitive gene-set test implemented with MAGMA. We replicated the SNP in in a meta-analysis of three independent OCD case/control genome-wide datasets (0.0069, cases=3384, controls=8363). Polygenic risk from OC traits was significantly associated with OCD in a sample of childhood-onset OCD and vice versa (’s<0.01). OC traits were highly but not significantly correlated with OCD ( =0.83, =0.07). We report the first replicated genome-wide significant variant for OCD traits. Our results indicate that OC traits in the general population share genetic risk with OCD in independent samples. This study demonstrates the feasibility and power of using trait-based approaches in community samples in psychiatric genomics.