In the context of genetic association testing, population stratification refers to systematic genetic differences between subpopulations. This is especially problematic in instances where the investigators are blind to the presence of stratification and/or the population substrata also differ phenotypically. In these instances, association analyses will be prone to generate spurious genotype-phenotype relationships and it is especially important in prevention trials to ensure that, even after the fact, randomization properly accounted for population stratification. Based on early results in the candidate gene era, this was thought to be a serious issue, and cause of the lack of replication in many candidate gene studies (Tabor, Risch, & Myers, 2002). Contradictory opinions notwithstanding (Hutchison, Stallings, McGeary, & Bryan, 2004), the availability of genome-wide SNP data made it very apparent that population structure or stratification was a potential source of spurious false positive results, even in samples thought to be homogeneous (Burton et al., 2007; Freedman et al., 2004). Several methods, including genomic control (Devlin & Roeder, 1999) and STRUCTURE (Pritchard & Rosenberg, 1999; Pritchard & Donnelly, 2001) are available to deal with this
