Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of sex (strong risk factor), life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across the models examined in this study. Moreover, these robust main effect results are consistent with the main effect results from the Caspi study that originally reported the interaction,16 with the re-examination of the topic using primary data by Risch et al.,23 and with prior meta-analyses.23–26 Based on our findings, we conclude that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not a broadly generalizable effect, but must be of modest effect size and only observable in limited situations. Our lack of replication coincides with findings of the Christchurch Health and Developmental Study,67 a prospective longitudinal birth-cohort, with measures, outcomes, and sample (both size and origin on the south island of
