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Impact of Population Stratification on Family-Based Association in an Admixed Population
T B Mersha1, L Ding1, H He2
1Divisions of Asthma Research, Biostatistics and Epidemiology, Human Genetics, and Physical Medicine and Rehabilitation and Center for Autoimmune Genomics and Etiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA ; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
Abstract:
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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