In 2003, Caspi and colleagues (17) reported an increasingly positive relationship between number of self-reported stressful life events and depression risk among individuals having more short alleles at the serotonin transporter (5-HTTLPR) polymorphism. Their study has been extremely influential, having tallied over 3,000 citations and a large number of replication attempts. We review this specific cG×E hypothesis and the attempts to replicate it because it highlights the important issue of direct compared with indirect replications and because it potentially illustrates the issues surrounding publication bias and false discovery rates discussed above.
