Association between the dopamine receptor D4 (DRD4) gene and obsessive‐compulsive disorder

Obsessive‐compulsive disorder (OCD) is a frequent and disabling anxiety disorder. Dopamine (DA) might be involved in its pathophysiology, therefore DA receptors are candidate genes in OCD. A 48‐base pairs (bp) polymorphism located in the third exon of the dopamine receptor type 4 (DRD4) gene has been described. Previous case control studies, however, have reported inconclusive results in OCD. The aim of the study was to study this polymorphism in a family‐based association study of 55 trios. Extended transmission‐disequilibrium test (ETDT) for preferential allele transmission in this group showed an absence of transmission of the allele 2 for the 48 bp repeat polymorphism of the DRD4 gene ( P  = 0.005). Moreover, in a population‐based association study, we found a significantly lower frequency of the allele 2 in patients suffering from OCD compared to ethnically‐matched controls ( P  = 0.02). We found no association of DRD4 48 bp polymorphism with OCD in the subgroup of patients with comorbid tics. This study is the first to report on a significant association of variants of the DRD4 gene in OCD, found on both family‐ and population‐based studies. The results suggest that the 2 allele or a nearby genetic variation could have a protective effect against OCD symptoms. © 2003 Wiley‐Liss, Inc.