Use of unlinked genetic markers to detect population stratification in association studies

We examine the issue of population stratification in association-mapping st udies. In case-control studies of association, population subdivision or re cent admixture of populations can lead to spurious associations between a p henotype and unlinked candidate loci. Using a model of sampling from a stru ctured population, we show that if population stratification exists, it can be detected by use of unlinked marker loci. We show that the case-control- study design, using unrelated control individuals, is a valid approach for association mapping, provided that marker loci unlinked to the candidate lo cus are included in the study, to test for stratification. We suggest guide lines as to the number of unlinked marker loci to use.