New approaches to disease mapping in admixed populations

Abstract

Admixed populations such as African Americans and Hispanic Americans are often medically underserved and bear a disproportionately high burden of disease. Owing to the diversity of their genomes, these populations have both advantages and disadvantages for genetic studies of complex phenotypes. Advances in statistical methodologies that can infer genetic contributions from ancestral populations may yield new insights into the aetiology of disease and may contribute to the applicability of genomic medicine to these admixed population groups.

Figure 1. Admixture leads to variation in genome-wide and local ancestry

a ∣ The variation in genome-wide ancestry in individuals from admixed populations is illustrated by using EIGENSOFT software to apply principal components analysis to admixed individuals. The samples were derived from HapMap 3 and the Human Genome Diversity Project (HGDP). The HapMap 3 samples included: West African (YRI, Yoruba in Ibadan, Nigeria), European (CEU, Utah residents with northern and western European ancestry from the CEPH collection), African American (ASW, African ancestry in Southwest USA) and Mexican American (MXL, Mexican ancestry in Los Angeles, California). For Native Americans, HGDP samples were used. Analyses were restricted to the intersection of HapMap 3 and HGDP marker sets. The results confirm that most African Americans lie on a cline of African and European ancestry with an average of 80% African and 20% European ancestry^,,. The results also confirm that Mexican Americans lie on a cline of European and Native American ancestry with low levels of African ancestry: an average of 50% European, 45% Native American and 5% African ancestry^,,. We caution that the positions of Native American individuals on this plot are complicated by recent European admixture (especially in Pima and Maya) and by population-specific drift (especially in Colombian, Karitiana and Surui populations). b ∣ Here, the variation in local ancestry in African Americans is illustrated by showing an individual (NA19919) from the ASW population as analysed by HAPMIX software to estimate local ancestry on chromosome 1. The lengths of chromosomal segments of 0, 1 or 2 copies of European ancestry are consistent with previous estimates of an average of six generations since admixture in this population^,,. We note that Latino populations have an average of 10–15 generations since admixture, leading to shorter chromosomal segments^,,.