and phenotypic measurements can also be standardized to a high degree, environmental exposure measurements vary markedly across studies (150). Two kinds of heterogeneity should be distinguished: heterogeneity in the types of stress exposure versus heterogeneity in the quality of exposure measurements. Regarding exposure types, stressful experiences come in many forms (Table 1 and Table 2) and studies of the 5-HTTLPR G×E have rightly gone beyond the original report to incorporate them. This environmental measurement heterogeneity has implications for matching the genetic model across studies, because the “correct” genetic model could vary depending on severity of the environmental exposure or other factors such as developmental stage and course of illness (e.g., first-onset versus recurrent depression). By insisting that all results must conform to one genetic model, the meta-analysis approach conceals potentially informative patterns, if they exist. Regarding measurement quality, in G×E research it is folly to give greater weight to larger samples, because many large samples are afflicted by poor exposure measurement. Overall, heterogeneity in both the type of stress exposures and in the quality of exposure measurements renders the studies in Table 1 and Table 2 inappropriate for drawing one simple conclusion about statistical replication (145).
