Population substructure is a well-known confounder in population-based case-control genetic studies, but its impact in family-based studies is unclear. We performed population substructure analysis using extended families of admixed population to evaluate power and Type I error in an association study framework. Our analysis shows that power was improved by 1.5% after principal components adjustment. Type I error was also reduced by 2.2% after adjusting for family substratification. The presence of population substructure was underscored by discriminant analysis, in which over 92% of individuals were correctly assigned to their actual family using only 100 principal components. This study demonstrates the importance of adjusting for population substructure in family-based studies of admixed populations.
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This work was partially supported by National Institutes of Health Grants K01HL103165, K23HD074683, and K25AG043546. The authors would like to thank the organizers of GAW18 for providing access to the dataset. The GAW18 whole-genome sequence data were provided by the T2D-GENES Consortium, which is supported by NIH Grants U01 DK085524, U01 DK085584, U01 DK085501, U01 DK085526, and U01 DK085545. The other genetic and phenotypic data for GAW18 were provided by the San Antonio Family Heart Study and San Antonio Family Diabetes/Gallbladder Study, which are supported by NIH Grants P01 HL045222, R01 DK047482, and R01 DK053889. The Genetic Analysis Workshop is supported by NIH Grant R01 GM031575.
Mersha, T. B.; Ding, L.; He, H.; Alexander, E. S.; Zhang, X.; Kurowski, B. G.; Pilipenko, V.; Kottyan, L.; Martin, L. J.; and Fardo, David W., "Impact of Population Stratification on Family-Based Association in an Admixed Population" (2015). Biostatistics Faculty Publications. 19.