Meta-analysis of the association between the catecholamine-O-methyl-transferase gene and obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is a chronic, severely debilitating mental illness that affects approximately 1-2% of the population. Data from twin and family studies have shown that genetic factors contribute to the expression of the disease. The dopaminergic system has been implicated in the pathogenesis of OCD, and catecholamine-O-methyl-transferase (COMT) is a key modulator of dopaminergic and noradrenergic neurotransmission. The gene for COMT has a common polymorphism that has been shown to be correlated with a three- to fourfold change in enzymatic activity. Several groups have searched for an association between the COMT gene polymorphism and the presence or absence of OCD, with contrasting results. We conducted a systematic review and meta-analysis of both the published literature and unpublished data. Available data were stratified according to the original study design as either case-control or family-based, and two separate meta-analyses were conducted, using both fixed-effects and random-effects models. These analyses showed insufficient evidence to support an association between the COMT gene polymorphism and OCD. Subgroup stratification based on gender generated no statistically significant associations. These results should be considered in any future work correlating the COMT gene with OCD. Copyright 2003 Wiley-Liss, Inc.