title: 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.
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.
  
  
  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.
authors.affiliation: Human Genetic Center, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Yu
authors.forename: Maja
authors.initials: M
authors.lastname: Barbalic
authors.forename: Ariel
authors.initials: A
authors.lastname: Brautbar
authors.forename: Vijay
authors.initials: V
authors.lastname: Nambi
authors.forename: Ron C
authors.initials: RC
authors.lastname: Hoogeveen
authors.forename: Weihong
authors.initials: W
authors.lastname: Tang
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mosley
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Christopher R
authors.initials: CR
authors.lastname: deFilippi
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: Sekar
authors.initials: S
authors.lastname: Kathiresan
authors.forename: Ken
authors.initials: K
authors.lastname: Rice
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
mesh_terms: D050197:Atherosclerosis / Q000097:blood* / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012111:Residence Characteristics; D012307:Risk Factors; D020107:Troponin T / Q000097:blood* / Q000235:genetics; D044465:White People / Q000235:genetics*
chemical_list: C498001:NCOA2 protein, human; D051958:Nuclear Receptor Coactivator 2; C545568:TNNT2 protein, human; D020107:Troponin T