This is the largest study to date to use consistent statistical analyses across all samples to examine the hypothesized interaction between 5-HTTLPR genotype and stress exposure affecting major depression. As detailed in our protocol,1 our design was based on consistent, de novo analyses chosen by a consensus of participating researchers in the field, with inclusion open to all researchers with published or unpublished data that met objective minimum participation criteria. The purpose was to address multiple issues of concern about previous meta-analyses of the topic: (i) heterogeneity of phenotypes, (ii) publication bias from small studies, (iii) heterogeneity of statistical models used to produce the input for the meta-analysis, (iv) meta-analysis models that did not take direction of effect into account.
