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 PTPRD (protein tyrosine phosphatase delta;) was associated with OC traits at the genome-wide significance level (p=2.48x10-8). A variant in GRID2 was significantly associated with only the symmetry/ordering dimension (p=3.2x10-8). 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: NPAS2 (p=7.8x10-7), GRID2 (p=1.6x10-6) and SH3GL2 (p=1.9x10-7). 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 PTPRD in a meta-analysis of three independent OCD case/control genome-wide datasets (p=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 (p