Genetic Determinants of Lipid Traits in Diverse Populations from the Population Architecture using Genomics and Epidemiology (PAGE) Study
Year: 2011
Type: review
Study design: Observational Study
Abstract: For the past five years, genome-wide association studies (GWAS) have identified hundreds of common variants associated with human diseases and traits, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels. Approximately 95 loci associated with lipid levels have been identified primarily among populations of European ancestry. The Population Architecture using Genomics and Epidemiology (PAGE) study was established in 2008 to characterize GWAS-identified variants in diverse population-based studies. We genotyped 49 GWAS-identified SNPs associated with one or more lipid traits in at least two PAGE studies and across six racial/ethnic groups. We performed a meta-analysis testing for SNP associations with fasting HDL-C, LDL-C, and ln(TG) levels in self-identified European American (~20,000), African American (~9,000), American Indian (~6,000), Mexican American/Hispanic (~2,500), Japanese/East Asian (~690), and Pacific Islander/Native Hawaiian (~175) adults, regardless of lipid-lowering medication use. We replicated 55 of 60 (92%) SNP associations tested in European Americans at p<0.05. Despite sufficient power, we were unable to replicate ABCA1 rs4149268 and rs1883025, CETP rs1864163, and TTC39B rs471364 previously associated with HDL-C and MAFB rs6102059 previously associated with LDL-C. Based on significance (p<0.05) and consistent direction of effect, a majority of replicated genotype-phentoype associations for HDL-C, LDL-C, and ln(TG) in European Americans generalized to African Americans (48%, 61%, and 57%), American Indians (45%, 64%, and 77%), and Mexican Americans/Hispanics (57%, 56%, and 86%). Overall, 16 associations generalized across all three populations. For the associations that did not generalize, differences in effect sizes, allele frequencies, and linkage disequilibrium offer clues to the next generation of association studies for these traits.
Source: PLoS Genetics
Authors: Logan Dumitrescu, Cara L. Carty, Kira Taylor, Fredrick R. Schumacher, Lucia A. Hindorff, José L. Ambite, Garnet Anderson, Lyle G. Best, Kristin Brown-Gentry, Petra Bůžková, Christopher S. Carlson, Barbara Cochran, Shelley A. Cole, Richard B. Devereux, Dave Duggan, Charles B. Eaton, Myriam Fornage, Nora Franceschini, Jeff Haessler, Barbara V. Howard, Karen C. Johnson, Sandra Laston, Laurence N. Kolonel, Elisa T. Lee, Jean W. MacCluer, Teri A. Manolio, Sarah A. Pendergrass, Miguel Quibrera, Ralph V. Shohet, Lynne R. Wilkens, Christopher A. Haiman, Loïc Le Marchand, Steven Buyske, Charles Kooperberg, Kari E. North, Dana C. Crawford
Institutions: Vanderbilt University, Fred Hutch Cancer Center, University of North Carolina at Chapel Hill, University of Southern California, National Institutes of Health, National Human Genome Research Institute, Missouri Breaks Industries Research (United States), University of Washington, Baylor College of Medicine, Texas Biomedical Research Institute, Weill Cornell Medicine, Translational Genomics Research Institute, Brown University, The University of Texas Health Science Center at Houston, MedStar Health Research Institute, University of Tennessee Health Science Center, University of Hawaii System, University of Hawaii Cancer Center, University of Oklahoma Health Sciences Center, University of Hawaiʻi at Mānoa, Rutgers, The State University of New Jersey
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: Vanderbilt University, Johns Hopkins University, Cedars-Sinai Medical Center, Strong, Ministerio de Economía y Competitividad, National Institutes of Health, Centers for Disease Control and Prevention, U.S. Public Health Service, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Center for Research Resources
Awards: CARDIA, G1028935811, G1045430581, Cardiovascular Disease in Sioux Indians, G118440752, G1188197595, G1220223050, G1241292848, Epidemiology of putative genuine genetic variant: The Women's Health Intiative, G1325221871, G1332411685, G136105103, G1462415530, CHS-ULTRASOUND READING, G153510172, CARDIA, The Strong Heart Study, Phase V, G1548097448, G1593340546, CORONARY HEART DISEASE AND STROKE, G1639455850, G1646017446, G164614106, MRI READING CENTER FOR THE CARDIOVASCULAR HEALTH STUDY, CARDIA, G1746001450, G1909643007, G191650467, Atherosclerosis Risk in Communities Study (ARIC), CARDIA-ECHOCARDIOGRAPHY READING, G215333750, G2189639697, G2194386449, G2215229, G2253702613, G2295046671, Epidemiology of Putative Causal Variants in the Multiethnic Cohort, G2404385439, G2417273319, CARDIA, CCSP FIELD CENTER, G2548880556, G2555954497, G2569189721, G2587248622, G25881238, COMMUNITY AND COHORT SURVEILLANCE PROGRAM, G277826483, G2786045897, G2800149121, CENTRAL HEMOSTATIS LABORATORY FOR CCSP, Strong Heart Family Study, G2852769941, G2868073770, G2899267414, G297113894, WGA Study to Identify Genetic Variants Associated with CV Events in CHS, G305513510, LONGITUDINAL STUDIES OF CORONARY HEART DISEASE RISK FACTORS IN YOUNG ADULTS, G3087775723, G3107571658, G3134865449, Cardiovascular Evaluation for the SHS Phase V, CORONARY ARTERY DISEASE RISK DEVELOPMENT IN YOUNG ADULTS, G3191277318, G3200378041, G3226848658, G3236609591, G328935669, G3396487927, G3544793024, G3642616392, G384035247, G390162502, NHLBI DNA Re-sequencing and Genotyping Program -- Genotyping Center, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, G4012114008, G4048755144, G4145745212, G4165892905, G4176762999, G4193739534, G4214622172, G4216744017, G423252844, G4281851297, Coronary Artery Risk Development in Young Adults (CARDIA) Study - Field Center, G4289235060, COORDINATING CENTER FOR WOMEN'S HEALTH INITIATIVE, G4302802884, G4401737188, G443405440, G4454202622, G4484576498, Atherosclerosis Risk in Communities Study (ARIC), G4560602636, G4671189754, G484043965, G4847987001, G4932516547, G4940723635, G4987078009, G5026349245, G50822097, G510023084, G5167412771, G5183277930, G5209003178, G5232982263, G528395701, G532295152, G5451084504, G5452216648, G5522185877, Atherosclerosis Risk in Communities Study (ARIC), G582705428, G5881391427, G589878898, CHS Events Follow-up Study, G603760282, G6203107232, G6204895930, G6226795708, G6279754272, Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3, G65159624, G6520056932, G6576172577, G6604908402, G6860406196, G687544517, G6918065631, G693077865, G7007046788, G709210845, G715477388, G7286144250, G7323080267, G7582705761, CHS RETINAL READING CENTER, General Clinical Research Center, G764651519, CARDIOVASCULAR HEALTH STUDY--ECHOCARDIOGRAPHY, G766700449, G786153652, Molecular Epidemiology of Nutrition and Cancer in the Multiethnic Cohort Study, G793702358, G7990718016, G7999488110, G806768229, G812579647, G8178424689, G8181733155, Epidemiologic Architecture for Genes Linked to Environment (EAGLE), G8399797517, G8486527673, G8546760883, G8593276544, G859984287, CHS-Transition Phase -268055222, G863538970, G8750984004, G8780700017, G8934942062, Cardiovascular Disease in Pima Indians, G9000007515, G9000015747, G9000027259, G9000028181, G9000028264, G9000039132, G9000069887, G9000072420, G9000076846, G9000080822, G9000108254, G9000112759, G9000121483, G9000124754, G9000126117, G9000140433, G9000145448, G9000152345, G9000155493, G9000195409, G9000205553, G9000239991, G9000294209, G9000350284, Diabetes Research Center (DRC), G905887895, G939135972, G960597250, Atherosclerosis Risk in Communities Study (ARIC), G999174792
OpenAlex ID: W2145269787