03504nas a2200505 4500008004100000022001400041245021500055210006900270260001300339300000900352490000600361520189100367653003902258653002002297653004002317653001102357653003402368653001102402653000902413653001602422653003502438653003602473653002402509653003002533653001702563653001502580100001302595700001902608700002002627700001702647700002202664700001802686700002202704700002202726700003002748700003002778700002202808700001402830700002302844700002802867700002002895700002102915710002602936856003602962 2013 eng d a1942-326800aAssociation 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.0 aAssociation of genomewide variation with highly sensitive cardia c2013 Feb a82-80 v63 a
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.
10aAfrican Continental Ancestry Group10aAtherosclerosis10aEuropean Continental Ancestry Group10aFemale10aGenome-Wide Association Study10aHumans10aMale10aMiddle Aged10aNuclear Receptor Coactivator 210aPolymorphism, Single Nucleotide10aProspective Studies10aResidence Characteristics10aRisk Factors10aTroponin T1 aYu, Bing1 aBarbalic, Maja1 aBrautbar, Ariel1 aNambi, Vijay1 aHoogeveen, Ron, C1 aTang, Weihong1 aMosley, Thomas, H1 aRotter, Jerome, I1 adeFilippi, Christopher, R1 aO'Donnell, Christopher, J1 aKathiresan, Sekar1 aRice, Ken1 aHeckbert, Susan, R1 aBallantyne, Christie, M1 aPsaty, Bruce, M1 aBoerwinkle, Eric1 aCARDIoGRAM consortium uhttps://chs-nhlbi.org/node/5857