Association of Genome-Wide Variation With Highly Sensitive Cardiac Troponin-T Levels in European Americans and Blacks
Year: 2012
Type: article
Study design: Observational Study
Abstract: BACKGROUND: High levels of cardiac troponin T, measured by a highly sensitive assay (hs-cTnT), are strongly associated with incident coronary heart disease and heart failure. To date, no large-scale genome-wide association study of hs-cTnT has been reported. We sought to identify novel genetic variants that are associated with hs-cTnT levels. METHODS AND RESULTS: We performed a genome-wide association in 9491 European Americans and 2053 blacks free of coronary heart disease and heart failure from 2 prospective cohorts: the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Genome-wide association studies were conducted in each study and race stratum. Fixed-effect meta-analyses combined the results of linear regression from 2 cohorts within each race stratum and then across race strata to produce overall estimates and probability values. The meta-analysis identified a significant association at chromosome 8q13 (rs10091374; P=9.06×10(-9)) near the nuclear receptor coactivator 2 (NCOA2) gene. Overexpression of NCOA2 can be detected in myoblasts. An additional analysis using logistic regression and the clinically motivated 99th percentile cut point detected a significant association at 1q32 (rs12564445; P=4.73×10(-8)) in the gene TNNT2, which encodes the cardiac troponin T protein itself. The hs-cTnT-associated single-nucleotide polymorphisms were not associated with coronary heart disease in a large case-control study, but rs12564445 was significantly associated with incident heart failure in Atherosclerosis Risk in Communities Study European Americans (hazard ratio=1.16; P=0.004). CONCLUSIONS: We identified 2 loci, near NCOA2 and in the TNNT2 gene, at which variation was significantly associated with hs-cTnT levels. Further use of the new assay should enable replication of these results.
Institutions: University of Maryland, Baltimore, Cedars-Sinai Medical Center, National Institutes of Health, University of Minnesota, Group Health Cooperative, Harvard University, Kaiser Permanente Washington Health Research Institute, Baylor College of Medicine, University of Washington, University of Mississippi Medical Center, Massachusetts General Hospital, National Heart, Lung, and Blood Institute, Framingham Heart Study, The University of Texas Health Science Center at Houston
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: Burroughs Wellcome Fund, National Institutes of Health, U.S. Public Health Service, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources, National Center for Advancing Translational Sciences
Awards: G1002540797, G1052397333, G109016790, G1135917780, G1177103769, G1220223050, G1243299691, G1332411685, G1345547317, G1462415530, CHS-ULTRASOUND READING, G1527150935, CORONARY HEART DISEASE AND STROKE, MRI READING CENTER FOR THE CARDIOVASCULAR HEALTH STUDY, G1691174148, UCLA Clinical and Translational Science Institute, G1727292203, G173303992, G1941623656, Genome-wide case-only study of antihypertensive drug-gene interactions, G2193588257, G2194386449, G236442059, G247538147, Institute for Clinical and Translational Research (UL1), Exceptional Survival: Trajectories to Functional Aging (CHS All Stars), G2555954497, G2663518188, G277826483, G2800149121, G2818629771, G2818913090, G297113894, WGA Study to Identify Genetic Variants Associated with CV Events in CHS, G3114902838, UCLA Clinical and Translational Science Institute, G328935669, G333228317, G3410686264, G3462919067, GWA for Gene-Environment Interaction Effects Influencing CHD, G395403786, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, Predictors of Alheimers Disease in Mild Cognitive Impairment, G4048755144, G423252844, G4429312988, Subcortical Hyperintensities in Sleep Apnea Syndrome, G457330776, G536099884, Genome-Wide Association for Loci Influencing CHD and Other Heart, Lung and Blood, G5488312170, Epidemiology of Venous Thrombosis and Pulmonary Embolism, G567847597, G573134505, CHS Events Follow-up Study, G61834786, G6226795708, Predictors of Alzheimers Disease in Mild Cognitive Impairment, G6548750934, CHS-Transition Phase, CHS RETINAL READING CENTER, CARDIOVASCULAR HEALTH STUDY--ECHOCARDIOGRAPHY, G777822606, CHS Events Follow-up Study, G7999488110, G8593276544, Diabetes Research Center (DRC), From GWAS loci to blood pressure genes, variants & mechanisms - Renewal, G905887895, G931818222
OpenAlex ID: W2024644137