Is serotonin transporter polymorphism (5-HTTLPR) allele status a predictor for obsessive-compulsive disorder? A meta-analysis

The serotonin transporter polymorphism has been implicated in obsessive-compulsive disorder (OCD). However, molecular genetic association studies have yielded inconsistent results. Variation may be due to lack of OCD subtype classification. The goal of this systematic review is to investigate the association of the S-allele of the serotonin transporter polymorphism with OCD and OCD subtypes. A total of 69 studies were initially found through a systematic search of the literature but only 13 with sufficient information to compute odds ratios were suitable for review. A total of 1991 participants with OCD and their 5-HTTLPR allele status were examined. The primary outcome measures were allele frequency and OCD diagnosis. A full meta-analysis was completed comparing the L- and S-alleles using a random effects model in RevMan 5.2.1. Further, a secondary meta-analysis stratified by sex and late-onset was conducted for S- versus L-allele frequency. In the primary meta-analysis, OCD was not associated with the S-allele of the 5-HTTLPR polymorphism (Z = 0.07, p = 0.94). Moreover, late-onset OCD was not associated with the S-allele (Z = 1.45, p = 0.15). However, when stratified by sex, there is an emerging sex-specific relationship. There was a trending association between the S-allele and OCD status in females (Z = 1.62, p = 0.10) but not in males (Z = 0.69, p = 0.49). The findings provide further support for the need of subtype classification of this heterogeneous disorder. Future studies should clearly examine sex differences and OCD age-of-onset. In particular, emphasis should be placed on the effect of female reproductive milestones on OCD onset and symptom exacerbation.