Box 1 What is admixture mapping?

Genetic admixture occurs when two or more populations that have been separated over long periods of history—often by geography—come into contact and intermix. For example, the genomes of many African-Americans, as members of one recently admixed population in the Americas, are a mosaic of variable proportions of what can be classified as European and West African ancestry (Reich et al. 2005). Admixture mapping relies on distinguishing these chromosomal segments of different ancestry, by the statistical enumeration of hundreds of ancestrally informative markers (AIMs) (Stephens et al. 1994; Collins-Schramm et al. 2002; Zhu et al. 2008). In recently admixed populations these ancestral segments are extremely long, requiring substantially fewer markers for scanning the entire genome than other whole genome association studies (GWAS). This characteristic makes admixture mapping more economical, more efficient, and theoretically a more powerful method for identifying common risk factors for complex disease (Stephens et al. 1994; McKeigue 1997; Collins-Schramm et al. 2002; Hoggart et al. 2004). However, admixture mapping only has statistical power to identify genetic variants that are differentially distributed across populations (Rife 1954; Chakraborty and Weiss 1988; Stephens et al. 1994; McKeigue 1997), and relatively few variants vary in frequency across human groups (Cavalli-Sforza and Piazza 1975; Jorde et al. 2001). Thus, admixture mapping is a more specialized method, and likely will only be useful for gene-hunting in a subset of complex diseases and traits. Nevertheless, the method has the potential for expansion and improvement. Most notably, many recently admixed groups exist worldwide, for which sets of informative AIMs—or admixture mapping panels—have not yet been constructed. Similarly, there are a considerable number of complex diseases which differ in prevalence across populations (McKeigue 1997; Smith and O’Brien 2005). In some cases, genetic factors may play a role. Thus, admixture mapping in combination with other methods may be of considerable use going forward.