No effect of the serotonin transporter on depression

One of the most famous examples of a gene-environment interaction is being scrutinized by evidence from one of the largest meta-analyses on the subject to date. There have been tons of reports claiming or refuting evidence for a statistically significant interaction between a variant in the serotonin transporter gene (5-HTT) and stressful life events and their effect on major depression. This article published this week in JAMA by several well-known geneticists (including Neil Risch and Kathleen Merikangas, authors of the highly influential 13-year old paper on why association may be more powerful than linkage) now provides evidence that no such interaction exists, and on top of that, there is no main effect of the serotonin transporter gene itself!

The authors performed a meta-analysis of 14 studies which published data on the association between 5-HTTLPR genotype (SS, SL, or LL), number of stressful life events (0, 1, 2, >3) or equivalent, and a categorical measure of depression. With a total sample size of 14,250 using a random-effects meta-analysis, no association was found for the interaction (OR, 1.01; 95% CI, 0.94-1.10), nor the transporter variant alone (OR, 1.05; 95% CI, 0.98-1.13).

On the other hand, the main effect association of stressful life events did hold up (OR, 1.41; 95% CI,1.25-1.57). So I suppose the bottom line here is if you want to avoid becoming depressed, then don't lose your job, gamble away your life savings, get a divorce, or brood over our inability to replicate a finding all weekend. Grab a cocktail, have a good weekend, and check back in a few years for the scoop on the genes.

JAMA: Interaction Between the Serotonin Transporter Gene (5-HTTLPR), Stressful Life Events, and Risk of Depression