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.
Yu, Bing MD, MSc; Barbalic, Maja PhD; Brautbar, Ariel MD; Nambi, Vijay MD; Hoogeveen, Ron C. PhD; Tang, Weihong PhD; Mosley, Thomas H. PhD; Rotter, Jerome I. MD; deFilippi, Christopher R. MD; O'Donnell, Christopher J. MD; Kathiresan, Sekar MD; Rice, Ken PhD; Heckbert, Susan R. MD, PhD; Ballantyne, Christie M. MD; Psaty, Bruce M. MD, PhD; Boerwinkle, Eric PhD
Circulation: Cardiovascular Genetics.
6(1):82-88, February 2013.
(Format: HTML, PDF)
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=9.06x10-9) 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=4.73x10-8) 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.
(C) 2013 American Heart Association, Inc.