Association studies of serotonin system candidate genes in early-onset obsessive-compulsive disorder

Background. Family-based evidence for association at serotonin system genes SLC6A4, HTR1B, HTR2A, and brain-derived neurotrophic factor (BDNF) has been previously reported in obsessive-compulsive disorder (OCD). Early-onset CCD is a more familial form of the disorder. Methods. We used the transmission-disequilibrium test of association at common polymorpbisms in each of these genes in 54 parent-child trios ascertained through probands with early-onset OCD. Results: No evidence for association was detected at any of the polymorpbisms in the entire set of subjects. Nominally significant association was,found at the HTR2A rs6311 polymorpbism in subjects with tic disorder and OCD (p =.05), replicating a previous finding in Tourette syndrome and OCD. Nominally significant association was also found for the SLC6A4 HT transporter gene-linked polymorphic region (5-HMPR) polymorpbism for female subjects (p =.03). Neither association would remain significant after statistical correction for multiple testing. Despite no individual study reporting replication, a pooled analysis of five replication studies of the SLC6A4 5-HTTLPR polymorphism supports association (p =.02). Conclusions. Low power across individual association studies in OCD may lead to a false acceptance of the null hypothesis. Accumulation of evidence from multiple studies will be necessary to evaluate the potential role for these genes in contributing to susceptibility to OCD.