Case-control studies of association in structured or admixed populations

Case-control tests for association are an important tool for mapping complex-trait genes. But population structure can invalidate this approach, leading to apparent associations at markers that are unlinked to disease loci. Family-based tests of association can avoid this problem, but such studies are often more expensive and in some cases--particularly for late-onset diseases--are impractical. In this review article we describe a series of approaches published over the past 2 years which use multilocus genotype data to enable valid case-control tests of association, even in the presence of population structure. These tests can be classified into two categories. "Genomic control" methods use the independent marker loci to adjust the distribution of a standard test statistic, while "structured association" methods infer the details of population structure en route to testing for association. We discuss the statistical issues involved in the different approaches and present results from simulations comparing the relative performance of the methods under a range of models.