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

Circ Cardiovasc Genet. 2013 Feb;6(1):82-8. doi: 10.1161/CIRCGENETICS.112.963058. Epub 2012 Dec 16.

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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural

MeSH terms

  • African Continental Ancestry Group / genetics*
  • Atherosclerosis / blood*
  • Atherosclerosis / genetics*
  • European Continental Ancestry Group / genetics*
  • Female
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Middle Aged
  • Nuclear Receptor Coactivator 2 / genetics
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Residence Characteristics
  • Risk Factors
  • Troponin T / blood*
  • Troponin T / genetics

Substances

  • NCOA2 protein, human
  • Nuclear Receptor Coactivator 2
  • TNNT2 protein, human
  • Troponin T

Grant support