the three analyses. Karg et al. included studies that Munafo et al. (38), Risch et al. (5), and we, in this report, consider to be indirect replications. For example, Karg et al. included studies investigating a wide range of alternative environmental stressors (e.g., hip fractures), alternative outcome measures (e.g., physical and mental distress), and alternative statistical models (e.g., dominant genetic models). Furthermore, 11 studies included in the Karg et al. analysis used “exposure only” designs that investigate only those individuals who have been exposed to the stressor. We excluded such designs in this review because they do not actually test interactions; rather, interactions must be inferred by assuming an opposite or no relationship between the risk allele and the outcome in nonexposed individuals. Additionally, the result from at least one of the studies deemed supportive of the interaction in Karg and colleagues's meta-analysis (40) is actually in the opposite direction of the original finding when the same statistical model employed in the original report is used (5). Taken together, the pattern of results emerging from these three meta- and mega-analyses is surprisingly consistent: direct replication attempts of the original finding have generally not been supportive, whereas indirect replication attempts generally
