Polygenicity, the small effects of individual loci, and the rarity of large-effect loci mean that the most critical requirement for successful genetic dissection of a psychiatric disorder is the availability of sufficiently large clinical cohorts, emphasized by the recent discoveries of the Psychiatric Genomics Consortium (PGC), whose collaborative large-scale approach has had a major impact on the field (3). However, there is an inherent practical tradeoff between sample size and the depth of phenotyping. Disorders with large environmental risk factors, such as anxiety and depression, may benefit from more attention to clinical phenotyping. Rigorous attention to the phenotype and screening for known and putative risk factors may increase the power to detect genetic effects, as evidenced by the recent CONVERGE GWAS in depression (22).
