TY - JOUR T1 - 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. JF - Circ Cardiovasc Genet Y1 - 2013 A1 - Yu, Bing A1 - Barbalic, Maja A1 - Brautbar, Ariel A1 - Nambi, Vijay A1 - Hoogeveen, Ron C A1 - Tang, Weihong A1 - Mosley, Thomas H A1 - Rotter, Jerome I A1 - deFilippi, Christopher R A1 - O'Donnell, Christopher J A1 - Kathiresan, Sekar A1 - Rice, Ken A1 - Heckbert, Susan R A1 - Ballantyne, Christie M A1 - Psaty, Bruce M A1 - Boerwinkle, Eric KW - African Continental Ancestry Group KW - Atherosclerosis KW - European Continental Ancestry Group KW - Female KW - Genome-Wide Association Study KW - Humans KW - Male KW - Middle Aged KW - Nuclear Receptor Coactivator 2 KW - Polymorphism, Single Nucleotide KW - Prospective Studies KW - Residence Characteristics KW - Risk Factors KW - Troponin T AB -

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.

VL - 6 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23247143?dopt=Abstract ER -