There are two distinct cultures vying to evaluate the worth of the 5-HTTLPR G×E findings: a purely statistical (theory-free) approach that relies wholly on meta-analysis (142, 143) versus a construct-validity (theory-guided) approach that looks for a nomological network of convergent evidence (this article). The statistical approach is essential for confirming direct genotype-phenotype association discoveries. This approach is driven by the imperative to avoid false positives when evaluating associations sifted from huge amounts of data in theory-free, genome-wide testing with nil prior probability of gene-disease association (144). Naturally, the statistical approach prizes exact replication. In the statistical approach, replication attempts’ elements should match the original report’s elements, including sample, phenotype, polymorphism, genetic model, and direction of effect. Larger samples are given greater weight in statistical evaluation, because with all other study elements held equal, power is decisive (145).
