Disorder-specific genetic factors in obsessive-compulsive disorder: A comprehensive meta-analysis

Much remains to be learned about the etiology of obsessive-compulsive disorder (OCD). Twin studies suggest that it arises from both disorder-specific and non-specific genetic factors. To understand the etiology of OCD per se, it is necessary to identify disorder-specific factors. Previous research shows that OCD is associated with serotonin-related polymorphisms (5-HTTLPR coded as triallelic and HTR2A rs6311/rs6313) and, in males, a polymorphism involved in catecholamine modulation; COMT (rs4680). The present study is the first comprehensive meta-analysis to investigate whether these polymorphisms are specific to OCD. A meta-analysis was conducted for genetic association studies of OCD or any other psychiatric disorder, published in any language, in any country. A total of 551 studies were examined, of which 290 were included, consisting of 47,358 cases and 68,942 controls from case control studies, and 2,443 trios from family based studies. The main meta-analysis was limited to those disorders in which there were at least five datasets (studies or sub-studies) per disorder. Results confirmed that OCD is associated with polymorphisms of 5-HTTLPR, HTR2A, and, in males only, COMT. These polymorphisms were not associated with almost all other forms of psychopathology, including unipolar mood disorders, bipolar disorder, panic disorder, schizophrenia, and alcohol dependence. OCD, compared to most other disorders, had a significantly stronger association with particular alleles of each of the polymorphisms. Results did not differ across ancestral groups (Asian vs. Caucasian), designs (case control vs. family based), or diagnostic systems. Results suggest that the polymorphisms investigated in this study are relatively specific to OCD.