Whole-Genome Association Analysis of Treatment Response from Obsessive-Compulsive Disorder

Abstract

Up to 30% of individuals with obsessive-compulsive disorder (OCD) display an inadequate response to serotonin reuptake inhibitors (SRIs). Genetic predictors of OCD treatment response have not been efficiently examined using a genome-wide association study (GWAS). In order to identify genetic variations that could potentially influence SRI response, a GWAS with 804 OCD patients containing information on SRI response was conducted. SRI response was used based on self-reported data and characterized as “response” (N = 514) or “non-response” (N = 290). The more powerful quasi-likelihood score (MQLS) test was used to conduct a genome-wide association test correcting for relatedness. An adjusted logistic model was then used to examine the effect size of the variants in probands. The most significant SNP found was rs17162912 (P = 1.76 × 10⁻⁸), which is near the gene DISP1 on 1q41–q42, a microdeletion region that has been implicated in neurological development. Six other SNPs showed evidence of association (P < 10⁻⁵): rs9303380, rs12437601, rs16988159, rs7676822, rs1911877, and rs723815. Two of the SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, are located near the PCDH10 gene and had p-values of 2.86 × 10⁻⁶ and 8.41 × 10⁻⁶, respectively. The 35 other variations with a p-value <10⁻⁴ are involved with multiple genes expressed in the brain, including BRIN2B, PCDH10, and GPC6. The enrichment analysis suggested that there may be genes that play a role in the glutamatergic neurotransmission system (FDR = 0.0097) and the serotonergic system (FDR = 0.0213). The results of this study could provide new insights into genetic mechanisms underlying treatment response in OCD, but studies with larger sample sizes and more detailed information on drug dosage, as well as treatment duration, are needed.