In any case, whether G×E studies can meet prerequisite standards for statistical meta-analysis is immaterial, since replicating a theory-free association is not the goal. The goal is to evaluate the construct validity of a theory-guided hypothesis (156). In contrast to the statistical approach, the construct validation approach prizes design heterogeneity (although it requires high-quality samples and measures) (157). Construct validation seeks “sturdy” findings (6), defined as results that emerge repeatedly despite variation in sample characteristics, phenotype measurement, and environmental exposure, and that are validated across human epidemiology, experimental neuroscience, and animal models. We have attempted to show that this is the case with evidence for the 5-HTT stress-sensitivity hypothesis.
