The potential for population structure to undermine inferences in case-control association studies has long been debated113 but limited empirical data have been available to assess the issue. Our study highlighted several loci, some known and some new, which demonstrate substantial geographical variation in allele frequencies across Britain (Table 1), most probably due to natural selection in ancestral populations. Outside these loci, the effects of population structure are relatively minor, and do not represent a major source of confounding, provided that individuals with appreciable non-European ancestry are excluded. Although these conclusions may not generalize to studies in other locations, this finding reinforces the logistical and economic benefits of the case-control design over alternatives (such as family-based association studies).
