American Journal of Medical Genetics Part B (Neuropsychiatric Genetics) 127B:85–89 (2004) Meta-Analysis of the Association Between a Serotonin Transporter Promoter Polymorphism (5-HTTLPR) and Anxiety-Related Personality Traits

Anxiety-related personality traits, such as NEO neuroticism and TCI/TPQ harm avoidance, have been shown to have significant genetic compo-nents. To date, however, no specific genetic vari-ants that contribute to these traits have been conclusively identified. At least 26 studies have investigated a putative association between a functional serotonin transporter promoter poly-morphism (5-HTTLPR) and anxiety-related person-ality traits. The results of these studies have been inconsistent with some studies finding evidence for an association, and others not. We performed a meta-analysis of all applicable studies investi-gating this association. In the overall analysis (N5,629 subjects), we found suggestive evidence for an association between the 5-HTTLPR short allele (s) and increased anxiety-related personal-ity trait scores (P 0.087). However, we also found strong evidence for heterogeneity. This hetero-geneity is largely explained by substantial varia-tion between the studies in the inventory used. When the analysis was stratified by inventory type, there was a significant association between 5-HTTLPR and NEO neuroticism (P0.000016), a non-significant association between 5-HTTLPR and TCI/TPQ harm avoidance (P0.166), and no association between 5-HTTLPR and other anxi-ety-related personality traits (P0.944). There was no evidence that these results were either due to publication bias or accounted for by any one single study. We conclude that there is a strong association between the serotonin trans-porter promoter variant and neuroticism as measured in the NEO personality inventory and that non-replications are largely due to small sample size and the use of different inventories