This review should not be taken as a call for skepticism about the G×E field in psychiatry. We believe that G×Es are likely to be common, and that they may well prove to be important or even central for understanding the etiology of psychiatric disorders. At issue is how to separate the wheat from the chaff: Which G×E findings are replicable and illuminating, and which are spurious and lead to wasted resources, false hope, and increased skepticism? Scientists investigating genetic main effects using genome-wide association methods have made minimizing false discoveries a central creed of their enterprise (10). Indeed, the benefits of comprehensive SNP coverage and a conservative alpha have yielded hundreds of robust and replicable genetic associations. Such genome-wide methods have been proposed for the study of G×Es (42) and will undoubtedly prove informative, but this is not the only solution. Rather, true progress in understanding G×Es in psychiatry requires investigators, reviewers, and editors to agree on standards that will increase certainty in reported results. By doing so, the second decade of G×E research in psychiatry can live up to the promises made by the first.
