The primary objective of the current study was to increase understanding of the role 5-HTTLPR might play as a moderator of the response to stress as it impacts depression. To address the complexities of this topic, we performed a collaborative meta-analysis of data available from the participating studies, both published and unpublished, using consistent de novo analyses and variables determined a priori as described in the pre-registered protocol.1 Our collaborative meta-analysis strategy, wherein the consortium worked to harmonize phenotypes across studies, to prioritize specific analyses a priori, and to apply identical de novo statistical analyses across all participating studies, provided a balance between maximizing sample size while minimizing heterogeneity. With this approach and the large number of contributing samples, we are well positioned to clarify the relationship between 5-HTTLPR, stress, and depression.
