Second, even if the same variant is present in diverse populations, allele frequencies might differ45,46, as has been seen at TCF7L2 and KCNQ1 in type 2 diabetes (Box 2). The particular histories of recombinations, mutations, and divergences of genealogical lineages in the various populations can influence the “mappability” of a variant, so that a variant might be more easily detectable in some populations than in others47,48 (Fig. 1). Populations with lower LD, in which correlations between genotypes extend over shorter distances along a chromosome, might be more suitable for finely localizing a risk variant once its genomic region has been identified, as the genomic distance from true risk variants of disease-associated markers is likely to be smaller in such populations49. Localization methods can potentially capitalize on LD differences across populations by identifying variants for which a causal relationship with disease underlies divergent patterns of association signals in a genomic region50.
