A Phenomics-Based Strategy Identifies Loci on APOC1, BRAP, and PLCG1 Associated with Metabolic Syndrome Phenotype Domains
Year: 2011
Type: article
Study design: Observational Study
Abstract: Despite evidence of the clustering of metabolic syndrome components, current approaches for identifying unifying genetic mechanisms typically evaluate clinical categories that do not provide adequate etiological information. Here, we used data from 19,486 European American and 6,287 African American Candidate Gene Association Resource Consortium participants to identify loci associated with the clustering of metabolic phenotypes. Six phenotype domains (atherogenic dyslipidemia, vascular dysfunction, vascular inflammation, pro-thrombotic state, central obesity, and elevated plasma glucose) encompassing 19 quantitative traits were examined. Principal components analysis was used to reduce the dimension of each domain such that >55% of the trait variance was represented within each domain. We then applied a statistically efficient and computational feasible multivariate approach that related eight principal components from the six domains to 250,000 imputed SNPs using an additive genetic model and including demographic covariates. In European Americans, we identified 606 genome-wide significant SNPs representing 19 loci. Many of these loci were associated with only one trait domain, were consistent with results in African Americans, and overlapped with published findings, for instance central obesity and FTO. However, our approach, which is applicable to any set of interval scale traits that is heritable and exhibits evidence of phenotypic clustering, identified three new loci in or near APOC1, BRAP, and PLCG1, which were associated with multiple phenotype domains. These pleiotropic loci may help characterize metabolic dysregulation and identify targets for intervention.
Source: PLoS Genetics
Authors: Christy L. Avery, Qianchuan He, Kari E. North, Jose L. Ambite, Eric Boerwinkle, Myriam Fornage, Lucia A. Hindorff, Charles Kooperberg, James B. Meigs, James S. Pankow, Sarah A. Pendergrass, Bruce M. Psaty, Marylyn D. Ritchie, Jerome I. Rotter, Kent D. Taylor, Lynne R. Wilkens, Gerardo Heiss, Dan Yu Lin
Institutions: University of North Carolina at Chapel Hill, University of Southern California, The University of Texas Health Science Center at Houston, National Institutes of Health, National Human Genome Research Institute, Fred Hutch Cancer Center, Harvard University, Massachusetts General Hospital, University of Minnesota, Vanderbilt University Medical Center, Group Health Cooperative, Kaiser Permanente Washington Health Research Institute, University of Washington, Cedars-Sinai Medical Center, University of Hawaiʻi at Mānoa, University of Hawaii System
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,043
Funders: U.S. Department of Health and Human Services, Northwestern University, Wake Forest University, University of Minnesota, University of Washington, Johns Hopkins University, Broad Institute, National Institutes of Health, Kaiser Foundation Research Institute, University of North Carolina at Chapel Hill, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences
Awards: CARDIA, G109231058, G1107292973, G1186962729, G1220223050, G1238898755, G1241292848, G1261793039, MESA, CORONARY HEART DISEASE AND STROKE, G1276754516, G1281726998, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, Epidemiology of putative genuine genetic variant: The Women's Health Intiative, G1325221871, G1407109571, G1409423729, G1469524250, CHS-ULTRASOUND READING, G150102659, G153510172, CARDIA, G1548097448, G156924709, G1593340546, CORONARY HEART DISEASE AND STROKE, G1617453120, G1639455850, G1640378483, G1646017446, G1648020610, MRI READING CENTER FOR THE CARDIOVASCULAR HEALTH STUDY, CARDIA, G1686417863, G1740741465, G1828964916, CORONARY HEART DISEASE AND STROKE IN PEOPLE AGED 65-84, G191650467, G1958863888, G200764819, G206718646, Atherosclerosis Risk in Communities Study (ARIC), G2144938473, CARDIA-ECHOCARDIOGRAPHY READING, G215333750, G2175624253, G2178492673, G2194386449, G2217057004, CORONARY HEART DISEASE AND STROKE IN PEOPLE AGED 65-84, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G2253702613, G2262782284, G2272251213, G2277026667, G2286437695, G2295046671, G2323469504, G2391884931, Epidemiology of Putative Causal Variants in the Multiethnic Cohort, G2417273319, MESA, CARDIA, G250621538, G2513955590, CCSP FIELD CENTER, G2547046739, G257474614, G25881238, G2602520260, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, COMMUNITY AND COHORT SURVEILLANCE PROGRAM, G2786045897, MESA, G2852769941, G2880260212, G2904493376, G296458788, G2982975052, G3042145041, G3045517347, LONGITUDINAL STUDIES OF CORONARY HEART DISEASE RISK FACTORS IN YOUNG ADULTS, G3093995152, G3107571658, CORONARY ARTERY DISEASE RISK DEVELOPMENT IN YOUNG ADULTS, G3236609591, G328935669, G3396487927, G34347772, G3444966432, G3544793024, Genetic Epidemiology of Causal Variants across the Life Course Phase II (CALiCo I, Multiethnic Cohort Study of Diet and Cancer, G3642616392, G3647016462, G3648845612, G3667269547, G3687594596, G3787787485, CANDIDATE GENE ASSOCIATION RESOURCE (CARE), MESA, G3906582721, G3990748671, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, G399481048, G4036023366, G4048755144, G4085988807, G4145745212, G4165892905, G4191938920, G4214622172, G4216744017, G423252844, G4281851297, Coronary Artery Risk Development in Young Adults (CARDIA) Study - Field Center, COORDINATING CENTER FOR WOMEN'S HEALTH INITIATIVE, TITLE: MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA), G4321061599, G4401650913, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-ULTRASOUND, G4454202622, Atherosclerosis Risk in Communities Study (ARIC), G4512137732, Enumerating the Community Burden of Heart Failure, G4560602636, G4587988226, G4617276643, G4762875940, G4798441548, G484043965, G4919155732, G4932516547, G4940723635, MESA, G5014201391, G5026578359, CARDIA, G50822097, G510023084, G5164707915, G5183277930, G528395701, G530368906, G532295152, G5402123591, Common Genetic Variation and Quantitative Diabetes Traits, G5452216648, G5522185877, G555506801, G5557719294, Epidemiology of Precursors to Type 2 Diabetes, G5654179670, G5787256936, G581887176, G582705428, G5835610291, G587882820, G589878898, CHS Events Follow-up Study, G603760282, G6095866717, G6203107232, G6204895930, G6211642071, G6226795708, G6338010018, G6359107525, The Framingham Heart Study, MESA, Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3, G6464247198, G6514094751, G6520056932, G6576172577, G66341962, G6670851527, G6817973296, G6918065631, G6948187022, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY, G7066869570, G7071300326, G715477388, G7176672723, G7272550893, G7323080267, MESA, G7582705761, CHS RETINAL READING CENTER, CARDIOVASCULAR HEALTH STUDY--ECHOCARDIOGRAPHY, G7651777114, G777822606, G786153652, Genetic Epidemiology of Causal Variants Across the Life Course, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--EBCT READING, Molecular Epidemiology of Nutrition and Cancer in the Multiethnic Cohort Study, G793702358, G7990718016, G7999488110, G812579647, A Genome-wide Association Study of Prostate Cancer in African Americans, Epidemiologic Architecture for Genes Linked to Environment (EAGLE), G8402048158, G8486527673, G8593276544, CHS-Transition Phase -268055222, G8769328942, G8780700017, G8934942062, G9000015747, G9000017360, G9000025517, G9000028181, G9000028264, G9000065698, G9000069887, G9000072420, G9000079831, G9000080822, G9000121483, G9000124008, G9000124674, G9000124754, G9000126117, G9000205553, G9000291067, G9000294005, G9000294209, G9000350284, TOPMed Omics of Type 2 Diabetes and Quantitative Traits, UNC Center for Environmental Health and Susceptibility, G905887895, Atherosclerosis Risk in Communities Study (ARIC), G991334795, G999174792
OpenAlex ID: W2145668898