Genome-wide association study of obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469 410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case–control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case–control analysis, the lowest two P -values were located within DLGAP1 ( P =2.49 × 10 −6 and P =3.44 × 10 −6 ), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3 , exceeded the genome-wide significance threshold with a P -value=3.84 × 10 −8 . However, when trios were meta-analyzed with the case–control samples, the P -value for this variant was 3.62 × 10 −5 , losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio–case–control sample, a significant enrichment of methylation QTLs ( P