While these studies are not exhaustive, they provide three insights into the functional architecture of complex disease. First, both low-and high-frequency risk alleles can independently exist within a single locus. Second, GWAS signals often map closely to underlying functional elements. Finally, the more general lack of variants with obvious functional consequences that would explain the association in GWAS regions suggests that sequencing of larger sample sets, as well as better functional annotation of regulatory elements, will be required.
