Meta-analysis confirms a functional polymorphism (5-HTTLPR) in the serotonin transporter gene conferring risk of bipolar disorder in European populations

Abstract

The serotonin transporter (5-HTT) is a candidate risk gene for bipolar disorder, and a functional polymorphism of 44-bp insertion/deletion (5-HTTLPR) located in the promoter region of this gene has been investigated for the association with the illness extensively among worldwide populations, but overall results were inconsistent and its role in the disorder remains unclear. The present study attempts to find its potential association with bipolar disorder using meta-analyzes that maximize the statistical power. We applied meta-analysis techniques by combining all available case–control studies of 5-HTTLPR and bipolar disorder in samples of European ancestry (with a total of 3778 cases and 4997 controls), and we assessed the evidence for allelic associations, heterogeneity among different studies, influence of each single study, and potential publication bias. The short allele (S allele) of 5-HTTLPR showed a significant association with bipolar disorder in our meta-analysis (odds ratio=1.10, p-value=0.005), suggesting it is likely a risk polymorphism for the illness, and the observed OR is consistent with other susceptibility loci identified through recent large-scale genetic association studies on bipolar disorder, which could be regarded simply as a small but detectable effects.