Title | Association of genome-wide variation with highly sensitive cardiac troponin-T levels in European Americans and Blacks: a meta-analysis from atherosclerosis risk in communities and cardiovascular health studies. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Yu, B, Barbalic, M, Brautbar, A, Nambi, V, Hoogeveen, RC, Tang, W, Mosley, TH, Rotter, JI, deFilippi, CR, O'Donnell, CJ, Kathiresan, S, Rice, K, Heckbert, SR, Ballantyne, CM, Psaty, BM, Boerwinkle, E |
Corporate Authors | CARDIoGRAM Consortium |
Journal | Circ Cardiovasc Genet |
Volume | 6 |
Issue | 1 |
Pagination | 82-8 |
Date Published | 2013 Feb |
ISSN | 1942-3268 |
Keywords | Atherosclerosis, Black People, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Nuclear Receptor Coactivator 2, Polymorphism, Single Nucleotide, Prospective Studies, Residence Characteristics, Risk Factors, Troponin T, White People |
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. |
DOI | 10.1161/CIRCGENETICS.112.963058 |
Alternate Journal | Circ Cardiovasc Genet |
PubMed ID | 23247143 |
PubMed Central ID | PMC3693561 |
Grant List | HHSN268201100009I / HL / NHLBI NIH HHS / United States R01 HL075366 / HL / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States HHSN268201100005I / HL / NHLBI NIH HHS / United States N01-HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States HL080295 / HL / NHLBI NIH HHS / United States UL 1RR033176 / RR / NCRR NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States HHSN268201100012C / HL / NHLBI NIH HHS / United States UL1RR025005 / RR / NCRR NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States HHSN268201100010C / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States HHSN268201100008C / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States HHSN268201100005G / HL / NHLBI NIH HHS / United States HHSN268201100008I / HL / NHLBI NIH HHS / United States HL085251 / HL / NHLBI NIH HHS / United States HHSN268201100007C / HL / NHLBI NIH HHS / United States HL105756 / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States R01 HL085251 / HL / NHLBI NIH HHS / United States R56 AG020098 / AG / NIA NIH HHS / United States HHSN268201100011I / HL / NHLBI NIH HHS / United States HHSN268201100011C / HL / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States AG-20098 / AG / NIA NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States HHSN268200625226C / / PHS HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States AG-027058 / AG / NIA NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States HL075366 / HL / NHLBI NIH HHS / United States HHSN268201100006C / HL / NHLBI NIH HHS / United States R01 AG020098 / AG / NIA NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States HHSN268201100009C / HL / NHLBI NIH HHS / United States HHSN268201100005C / HL / NHLBI NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States HHSN268201100007I / HL / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01-HC-85239 / HC / NHLBI NIH HHS / United States AG-023629 / AG / NIA NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States R01 AG027058 / AG / NIA NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States R56 AG023629 / AG / NIA NIH HHS / United States |
Association of genome-wide variation with highly sensitive cardiac troponin-T levels in European Americans and Blacks: a meta-analysis from atherosclerosis risk in communities and cardiovascular health studies.
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