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.

TitleAssociation 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 TypeJournal Article
Year of Publication2013
AuthorsYu, 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 AuthorsCARDIoGRAM Consortium
JournalCirc Cardiovasc Genet
Volume6
Issue1
Pagination82-8
Date Published2013 Feb
ISSN1942-3268
KeywordsAfrican Continental Ancestry Group, Atherosclerosis, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Nuclear Receptor Coactivator 2, Polymorphism, Single Nucleotide, Prospective Studies, Residence Characteristics, Risk Factors, Troponin T
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.

DOI10.1161/CIRCGENETICS.112.963058
Alternate JournalCirc Cardiovasc Genet
PubMed ID23247143
PubMed Central IDPMC3693561
Grant ListAG-023629 / AG / NIA NIH HHS / United States
AG-027058 / AG / NIA NIH HHS / United States
AG-15928 / AG / NIA NIH HHS / United States
AG-20098 / AG / NIA NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
HHSN268201100005C / / PHS HHS / United States
HHSN268201100006C / / PHS HHS / United States
HHSN268201100007C / / PHS HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100009C / / PHS HHS / United States
HHSN268201100010C / / PHS HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
HL075366 / HL / NHLBI NIH HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
HL085251 / HL / NHLBI NIH HHS / United States
HL087652 / HL / NHLBI NIH HHS / United States
HL105756 / HL / NHLBI NIH HHS / United States
N01-HC-15103 / HC / NHLBI NIH HHS / United States
N01-HC-35129 / HC / NHLBI NIH HHS / United States
N01-HC-45133 / HC / NHLBI NIH HHS / United States
N01-HC-55222 / HC / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01-HC-85239 / HC / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
UL 1RR033176 / RR / NCRR NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States