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

Bing Yu, Maja Barbalic, Ariel Brautbar, Vijay Nambi, Ron C. Hoogeveen, Weihong Tang, Thomas H. Mosley, Jerome I. Rotter, Christopher R. DeFilippi, Christopher J. O'Donnell, Sekar Kathiresan, Ken Rice, Susan R. Heckbert, Christie M. Ballantyne, Bruce M. Psaty, Eric Boerwinkle

Research output: Contribution to journalReview articlepeer-review

17 Scopus citations

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 casecontrol 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 hscTnT levels. Further use of the new assay should enable replication of these results.

Original languageEnglish (US)
Pages (from-to)82-88
Number of pages7
JournalCirculation: Cardiovascular Genetics
Volume6
Issue number1
DOIs
StatePublished - Feb 2013

Keywords

  • Genetics
  • Genome-wide association study
  • Troponin

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