Common variants of HTR3 genes are associated with obsessive-compulsive disorder and its phenotypic expression

Evidence from literature supports the existence of associations between serotonin-related genetic variants and obsessive-compulsive disorder (OCD), but few studies have explored the involvement of serotonin receptor type 3 genes (HTR3) in OCD. To identify whether HTR3 variability affects an individual's susceptibility to OCD, we examined 10 HTR3 variants in 596 individuals with OCD and 599 controls. A significant difference existed in the genotypic distribution of the HTR3B variant rs1176744 between individuals with OCD and controls (odds ratio [OR] = 0.74, 95% confidence interval [CI] = 0.60-0.91, P = 0.0043). A protective haplotype in HTR3B was also associated with OCD (OR = 0.77, CI = 0.63-0.95, permutated P = 0.0179). Analyses of OCD sub-phenotypes demonstrated significant associations between rs3758987 and early onset OCD in male subjects (OR = 0.49, CI = 0.31-0.79, P = 0.0031) and among rs6766410, rs6443930, and the cleaning dimension in female subjects (OR = 0.36, CI = 0.18-0.69, P = 0.0016 and OR = 0.47, CI = 0.29-0.79, P = 0.0030, respectively). Additionally, rs6766410 was related to contamination-based disgust in OCD (P = 0.0044). These results support that common HTR3 variants are involved in OCD and some of its clinical phenotypes.