The case for employing diverse populations in GWA studies has recently been strengthened by the observation that the proportion of phenotypic variation explained by variants discovered through GWA is typically small53. GWA studies have focused on common variants, alleles that were typically present in ancestral African populations and that spread worldwide with ancient human migrations. Rare variants, which have not been examined to the same extent, provide one possible genetic source for unexplained phenotypic variation54,55,56. They might even be responsible for some association signals currently attributed to common variants47,57. Because rare variants are usually more recent in origin, not having had enough time to increase in frequency and become common, they are more likely to be geographically localized, so that separate populations are more likely to differ in their collections of rare alleles than in their collections of common alleles (Fig. 2).
