Dopamine D3 receptor gene is associated with obsessive-compulsive disorder and antidepressant response

Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disorder with a strong genetic component. Previous studies have suggested a role for the dopamine receptor genes in OCD with the dopamine D3 receptor (DRD3) gene being relatively overlooked. There is neurobiological evidence that D3 may be involved in the striatal-cortical circuits that affect compulsive behaviour and anxiety. Thus, we investigated genetic variants of DRD3 in association with OCD and serotonin reuptake inhibitor (SRI) response.

We examined nine polymorphisms across DRD3 in 318 individuals with OCD (comprised of 129 small nuclear families, and 196 independent singleton cases) compared to 196 healthy controls matched for age, gender, and ethnicity using the family-based association test (FBAT) and case-control analysis respectively. Quantitative analyses were performed with age at onset (AAO) and Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) severity scores.

Nominally significant biased transmission of alleles in polymorphic sites rs2399504, rs7611535, rs1394016, Ser9Gly, rs167770, and rs2087017 was observed with FBAT. The rs2399504, rs7611535, rs1394016, Ser9Gly, and rs167770 polymorphisms were associated with AAO but not with Y-BOCS scores using FBAT. Five polymorphisms (rs2399504, rs7611535, rs1394016, Ser9Gly, and rs167770) showed a trend in case-control analyses for allele/genotype distributions. Haplotype analyses of the polymorphisms using Haploview revealed several combinations of markers associated with OCD. Nominally positive association between rs167770 and rs11721264 and sertraline response remained significant after correction for multiple testing.

This is the first report to our knowledge of involvement of DRD3 in OCD, which requires further research.