The Potential for Enhancing the Power of Genetic Association Studies in African Americans through the Reuse of Existing Genotype Data
Year: 2010
Type: article
Abstract: We consider the feasibility of reusing existing control data obtained in genetic association studies in order to reduce costs for new studies. We discuss controlling for the population differences between cases and controls that are implicit in studies utilizing external control data. We give theoretical calculations of the statistical power of a test due to Bourgain et al (Am J Human Genet 2003), applied to the problem of dealing with case-control differences in genetic ancestry related to population isolation or population admixture. Theoretical results show that there may exist bounds for the non-centrality parameter for a test of association that places limits on study power even if sample sizes can grow arbitrarily large. We apply this method to data from a multi-center, geographically-diverse, genome-wide association study of breast cancer in African-American women. Our analysis of these data shows that admixture proportions differ by center with the average fraction of European admixture ranging from approximately 20% for participants from study sites in the Eastern United States to 25% for participants from West Coast sites. However, these differences in average admixture fraction between sites are largely counterbalanced by considerable diversity in individual admixture proportion within each study site. Our results suggest that statistical correction for admixture differences is feasible for future studies of African-Americans, utilizing the existing controls from the African-American Breast Cancer study, even if case ascertainment for the future studies is not balanced over the same centers or regions that supplied the controls for the current study.
Source: PLoS Genetics
Institutions: USC Norris Comprehensive Cancer Center, University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, Cancer Prevention Institute of California, Stanford Medicine, Stanford Cancer Institute, Stanford University, Roswell Park Comprehensive Cancer Center, City Of Hope National Medical Center, City of Hope, Beckman Research Institute, Vanderbilt University, Vanderbilt Health, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, University of Miami, Sylvester Comprehensive Cancer Center, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Rutgers Cancer Institute
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: U.S. Department of Defense, Breast Cancer Research Foundation, Kenneth T. and Eileen L. Norris Foundation, California Breast Cancer Research Program, University of Southern California, University of Pittsburgh, Ministerio de Economía y Competitividad, National Institutes of Health, U.S. Army, National Cancer Institute, National Institute of Environmental Health Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Medical Research and Materiel Command
Awards: G1017297203, G1152199635, G1253072103, G153510172, G1569999668, G164076637, G1702743405, G1722492350, G1767941747, G1798569254, G2108445782, G2313542652, VITAMIN D RECEPTOR GENE POLYMORPHISM AND BREAST CANCER, G2407663899, G2548880556, G2646530656, G299563851, G3120360579, G3157549237, G3397471690, G422195599, G4407166175, G443607800, G4816767106, G4907478063, The Nashville Breast Health Study, G5528430224, G5654214539, G6272687058, G6289736641, G6554032491, G7646998162, G77261304, G8332978792, G870117454, G8820111440, G9000032209, G9000061634, G9000073604, G9000123264, G9000131094, G9000179242, G9000182874, G9000216949, G9000286278, G9000355445, G908924418, G921773184
OpenAlex ID: W2004141146