Genomic variation associated with mortality among adults of European and African ancestry with heart failure: the cohorts for heart and aging research in genomic epidemiology consortium.

TitleGenomic variation associated with mortality among adults of European and African ancestry with heart failure: the cohorts for heart and aging research in genomic epidemiology consortium.
Publication TypeJournal Article
Year of Publication2010
AuthorsMorrison, AC, Felix, JF, L Cupples, A, Glazer, NL, Loehr, LR, Dehghan, A, Demissie, S, Bis, JC, Rosamond, WD, Aulchenko, YS, Wang, YA, Haritunians, T, Folsom, AR, Rivadeneira, F, Benjamin, EJ, Lumley, T, Couper, D, Stricker, BH, O'Donnell, CJ, Rice, KM, Chang, PP, Hofman, A, Levy, D, Rotter, JI, Fox, ER, Uitterlinden, AG, Wang, TJ, Psaty, BM, Willerson, JT, van Duijn, CM, Boerwinkle, E, Witteman, JCM, Vasan, RS, Smith, NL
JournalCirc Cardiovasc Genet
Volume3
Issue3
Pagination248-55
Date Published2010 Jun
ISSN1942-3268
KeywordsAfrican Americans, Aged, Aged, 80 and over, Chemokines, Cohort Studies, European Continental Ancestry Group, Female, Genome-Wide Association Study, Genotype, Heart Failure, Humans, Introns, Male, MARVEL Domain-Containing Proteins, Membrane Proteins, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors
Abstract

BACKGROUND: Prognosis and survival are significant concerns for individuals with heart failure (HF). To better understand the pathophysiology of HF prognosis, the association between 2,366,858 single-nucleotide polymorphisms (SNPs) and all-cause mortality was evaluated among individuals with incident HF from 4 community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study.METHODS AND RESULTS: Participants were 2526 individuals of European ancestry and 466 individuals of African ancestry who experienced an incident HF event during follow-up in the respective cohorts. Within each study, the association between genetic variants and time to mortality among individuals with HF was assessed by Cox proportional hazards models that included adjustment for sex and age at the time of the HF event. Prospective fixed-effect meta-analyses were conducted for the 4 study populations of European ancestry (N=1645 deaths) and for the 2 populations of African ancestry (N=281 deaths). Genome-wide significance was set at P=5.0x10(-7). Meta-analytic findings among individuals of European ancestry revealed 1 genome-wide significant locus on chromosome 3p22 in an intron of CKLF-like MARVEL transmembrane domain containing 7 (CMTM7, P=3.2x10(-7)). Eight additional loci in individuals of European ancestry and 4 loci in individuals of African ancestry were identified by high-signal SNPs (P<1.0x10(-5)) but did not meet genome-wide significance.CONCLUSIONS: This study identified a novel locus associated with all-cause mortality among individuals of European ancestry with HF. This finding warrants additional investigation, including replication, in other studies of HF.

DOI10.1161/CIRCGENETICS.109.895995
Alternate JournalCirc Cardiovasc Genet
PubMed ID20400778
PubMed Central IDPMC3033765
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
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UL1 RR025005 / RR / NCRR NIH HHS / United States
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M01RR00425-39 / RR / NCRR NIH HHS / United States
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HHSN268200625226C / / PHS HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
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M01 RR000425-36 / RR / NCRR NIH HHS / United States
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