Priya B Shetty1, Hua Tang1, Tao Feng1, Bamidele Tayo1, Alanna C Morrison1, Sharon L R Kardia1, Craig L Hanis1, Donna K Arnett1, Steven C Hunt1, Eric Boerwinkle1, Dabeeru C Rao1, Richard S Cooper1, Neil Risch1, Xiaofeng Zhu2. 1. From the Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH (P.B.S., T.F., X.Z.); Department of Genetics, Stanford University School of Medicine, Stanford, CA (H.T.); Department of Public Health Sciences, Loyola University of Chicago Stritch School of Medicine, Maywood, IL (B.T., R.S.C.); Division of Epidemiology, Human Genetics and Environmental Sciences, The University of Texas Health Science Center at Houston School of Public Health (A.C.M., C.L.H., E.B.); Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor (S.L.R.K.); Department of Epidemiology, University of Alabama at Birmingham School of Public Health (D.K.A.); Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (S.C.H.); Division of Biostatistics, Washington University in St. Louis School of Medicine, St. Louis, MO (D.C. Rao); and Department of Epidemiology and Biostatistics, University of California, San Francisco (N.R.). 2. From the Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, Cleveland, OH (P.B.S., T.F., X.Z.); Department of Genetics, Stanford University School of Medicine, Stanford, CA (H.T.); Department of Public Health Sciences, Loyola University of Chicago Stritch School of Medicine, Maywood, IL (B.T., R.S.C.); Division of Epidemiology, Human Genetics and Environmental Sciences, The University of Texas Health Science Center at Houston School of Public Health (A.C.M., C.L.H., E.B.); Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor (S.L.R.K.); Department of Epidemiology, University of Alabama at Birmingham School of Public Health (D.K.A.); Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City (S.C.H.); Division of Biostatistics, Washington University in St. Louis School of Medicine, St. Louis, MO (D.C. Rao); and Department of Epidemiology and Biostatistics, University of California, San Francisco (N.R.). Xiaofeng.Zhu@case.edu.
Abstract
BACKGROUND: Admixture mapping of lipids was followed-up by family-based association analysis to identify variants for cardiovascular disease in African Americans. METHODS AND RESULTS: The present study conducted admixture mapping analysis for total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. The analysis was performed in 1905 unrelated African American subjects from the National Heart, Lung and Blood Institute's Family Blood Pressure Program (FBPP). Regions showing admixture evidence were followed-up with family-based association analysis in 3556 African American subjects from the FBPP. The admixture mapping and family-based association analyses were adjusted for age, age(2), sex, body mass index, and genome-wide mean ancestry to minimize the confounding caused by population stratification. Regions that were suggestive of local ancestry association evidence were found on chromosomes 7 (low-density lipoprotein cholesterol), 8 (high-density lipoprotein cholesterol), 14 (triglycerides), and 19 (total cholesterol and triglycerides). In the fine-mapping analysis, 52 939 single-nucleotide polymorphisms (SNPs) were tested and 11 SNPs (8 independent SNPs) showed nominal significant association with high-density lipoprotein cholesterol (2 SNPs), low-density lipoprotein cholesterol (4 SNPs), and triglycerides (5 SNPs). The family data were used in the fine-mapping to identify SNPs that showed novel associations with lipids and regions, including genes with known associations for cardiovascular disease. CONCLUSIONS: This study identified regions on chromosomes 7, 8, 14, and 19 and 11 SNPs from the fine-mapping analysis that were associated with high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides for further studies of cardiovascular disease in African Americans.
BACKGROUND: Admixture mapping of lipids was followed-up by family-based association analysis to identify variants for cardiovascular disease in African Americans. METHODS AND RESULTS: The present study conducted admixture mapping analysis for total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. The analysis was performed in 1905 unrelated African American subjects from the National Heart, Lung and Blood Institute's Family Blood Pressure Program (FBPP). Regions showing admixture evidence were followed-up with family-based association analysis in 3556 African American subjects from the FBPP. The admixture mapping and family-based association analyses were adjusted for age, age(2), sex, body mass index, and genome-wide mean ancestry to minimize the confounding caused by population stratification. Regions that were suggestive of local ancestry association evidence were found on chromosomes 7 (low-density lipoprotein cholesterol), 8 (high-density lipoprotein cholesterol), 14 (triglycerides), and 19 (total cholesterol and triglycerides). In the fine-mapping analysis, 52 939 single-nucleotide polymorphisms (SNPs) were tested and 11 SNPs (8 independent SNPs) showed nominal significant association with high-density lipoprotein cholesterol (2 SNPs), low-density lipoprotein cholesterol (4 SNPs), and triglycerides (5 SNPs). The family data were used in the fine-mapping to identify SNPs that showed novel associations with lipids and regions, including genes with known associations for cardiovascular disease. CONCLUSIONS: This study identified regions on chromosomes 7, 8, 14, and 19 and 11 SNPs from the fine-mapping analysis that were associated with high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides for further studies of cardiovascular disease in African Americans.
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