Two meta-analyses found no evidence for an interaction (Munafò et al., 2009, Risch et al., 2009), while one meta-analysis concluded that there was an effect (Karg et al., 2011). The difference lies in the way studies were selected for the meta-analyses. The authors of the positive GxE meta-analysis take the view that the effect of GxE is broad: “rather than focus on a specific class of studies, we sought to perform a meta-analysis on the entire body of work assessing the relationship between 5-HTTLPR, stress, and MD” (Karg et al., 2011). The one study that came closest to replicating the original design, a longitudinal study of a birth cohort in New Zealand, failed to replicate the first report (Fergusson et al., 2011). All that we can reasonably conclude is that current attempts to subdivide MD on the basis of interactions with environmental effects using candidate genes are unlikely to yield quick insights into the origins of the disease.
