Next-generation genome-wide association studies: time to focus on phenotype?

As investigators plan the next round of genome-wide association studies (GWAS), cohorts of more than 100 000 individuals are being proposed as the solution to the “missing heritability” from first-generation studies.1–6 Although such studies will undoubtedly reveal many additional common alleles contributing to human disease, consideration of the intrinsic design of GWAS, our knowledge of the genetic architecture of disease and the results of GWAS to date suggests that complementary strategies will be necessary to uncover all of the heritability.