title: Estimating kinship in admixed populations.
abstract: Genome-wide association studies (GWASs) are commonly used for the mapping of genetic loci that influence complex traits. A problem that is often encountered in both population-based and family-based GWASs is that of identifying cryptic relatedness and population stratification because it is well known that failure to appropriately account for both pedigree and population structure can lead to spurious association. A number of methods have been proposed for identifying relatives in samples from homogeneous populations. A strong assumption of population homogeneity, however, is often untenable, and many GWASs include samples from structured populations. Here, we consider the problem of estimating relatedness in structured populations with admixed ancestry. We propose a method, REAP (relatedness estimation in admixed populations), for robust estimation of identity by descent (IBD)-sharing probabilities and kinship coefficients in admixed populations. REAP appropriately accounts for population structure and ancestry-related assortative mating by using individual-specific allele frequencies at SNPs that are calculated on the basis of ancestry derived from whole-genome analysis. In simulation studies with related individuals and admixture from highly divergent populations, we demonstrate that REAP gives accurate IBD-sharing probabilities and kinship coefficients. We apply REAP to the Mexican Americans in Los Angeles, California (MXL) population sample of release 3 of phase III of the International Haplotype Map Project; in this sample, we identify third- and fourth-degree relatives who have not previously been reported. We also apply REAP to the African American and Hispanic samples from the Women's Health Initiative SNP Health Association Resource (WHI-SHARe) study, in which hundreds of pairs of cryptically related individuals have been identified.
authors: Department of Biostatistics, University of Washington, Seattle, 98195, USA. tathornt@u.washington.edu
authors: Timothy
authors: T
authors: Thornton
authors: Hua
authors: H
authors: Tang
authors: Thomas J
authors: TJ
authors: Hoffmann
authors: Heather M
authors: HM
authors: Ochs-Balcom
authors: Bette J
authors: BJ
authors: Caan
authors: Neil
authors: N
authors: Risch
mesh_terms: D001741:Black or African American / Q000235:genetics; D044466:Asian People; D005260:Female; D015894:Genome, Human; D055106:Genome-Wide Association Study; D060148:HapMap Project; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007198:Indians, North American; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D044382:Population Groups / Q000235:genetics*; D013223:Statistics as Topic; D044465:White People / Q000235:genetics