GWAS will probably remain an efficient way of investigating the remaining heritability, because their association signals may well define the genomic regions where rare variants, structural variants, and other forms of underlying variation are likely to cluster. The value of future studies can be enhanced by expanding to non-European samples and less common diseases and including more precise phenotypes and measures of environmental exposures48,68 (Box 3). Information on lower frequency alleles emerging from projects such as the 1,000 Genomes will be used to produce even more comprehensive GWA arrays, and will facilitate the investigation of the lower frequency spectrum without the need for de novo sequencing.
