There is an ongoing debate about what role, if any, 5-HTTLPR variation plays in depression. Various studies have argued for (e.g., [15]) or against (e.g., [46]) the proposition that an interaction between 5-HTTLPR variation and stressful life events alters the subsequent risk of depression. Both individual studies and meta-analyses of published results have come to differing conclusions. Numerous issues may contribute to the conflicting results including: heterogeneity among studies (varying study populations, varying definitions of depression, varying measures of stress, prospective versus retrospective assessments, varying analytical models); issues regarding timing of stress and depression; underpowered samples; and publication bias. To address the numerous complexities of the topic of the potential impact of 5-HTTLPR variation on depression, hypothesized as a moderator of the response to stress, we have designed a coordinated meta-analysis that performs consistent, de novo analyses of all available primary data, utilizing variables that are harmonized across the datasets and with analyses that were determined a priori. These analyses will be implemented in a set of primary analyses, arising from the original report of a GxE interaction involving 5-HTTLPR
