The success of exome sequencing in Mendelian disease genetics32 and the discovery of rare and low-frequency disease-associated variants in genes associated with complex diseases27,33,34 strongly support the hypothesis that, in addition to factors such as epistasis35,36 and gene-environment interactions37, many additional genetic risk factors of substantial effect size remain to be discovered through studies of rare variation. The data generated by the 1000 Genomes Project not only aid the interpretation of all genetic association studies, but also provide lessons on how best to design and analyse sequencing-based studies of disease.
