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We found from our analysis of the Genetic Analysis Workshop 17 data that the population structure of the 697 unrelated individuals was an important confounding factor for association studies, even if it was not explicitly considered when simulating the phenotypes. We uncovered structures beyond the reported ethnicities and found ample evidence of phenotype–population structure associations. The first 10 principal components of the genotype data of the 697 individuals demonstrated much stronger associations with Q1, Q2, and the disease than did the individuals’ ethnicities. In addition, we observed that population structure was a confounding factor for the Q1-gene association when identifying the significant genes both with and without adjusting for the causal single-nucleotide polymorphisms, the ethnicities, and the principal components. Many false discoveries remained after adjusting for the causal single-nucleotide polymorphisms. Adjusting for the principal components appeared more effective than did adjusting for ethnicity in terms of preventing false discoveries. This analysis was performed with knowledge of the causal loci.

Interrogating population structure and its impact on association tests