Title | Association of genome-wide variation with the risk of incident heart failure in adults of European and African ancestry: a prospective meta-analysis from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | Smith NL, Felix JF, Morrison AC, Demissie S, Glazer NL, Loehr LR, L Cupples A, Dehghan A, Lumley T, Rosamond WD, Lieb W, Rivadeneira F, Bis JC, Folsom AR, Benjamin E, Aulchenko YS, Haritunians T, Couper D, Murabito J, Wang YA, Stricker BH, Gottdiener JS, Chang PP, Wang TJ, Rice KM, Hofman A, Heckbert SR, Fox ER, O'Donnell CJ, Uitterlinden AG, Rotter JI, Willerson JT, Levy D, van Duijn CM, Psaty BM, Witteman JCM, Boerwinkle E, Vasan RS |
Journal | Circ Cardiovasc Genet |
Volume | 3 |
Issue | 3 |
Pagination | 256-66 |
Date Published | 2010 Jun |
ISSN | 1942-3268 |
Keywords | African Americans, Aged, Aged, 80 and over, Cohort Studies, Endopeptidases, Female, Genome-Wide Association Study, Heart Failure, Humans, Incidence, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk, Ubiquitin-Specific Proteases, Whites |
Abstract | BACKGROUND: Although genetic factors contribute to the onset of heart failure (HF), no large-scale genome-wide investigation of HF risk has been published to date. We have investigated the association of 2,478,304 single-nucleotide polymorphisms with incident HF by meta-analyzing data 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: Eligible participants for these analyses were of European or African ancestry and free of clinical HF at baseline. Each study independently conducted genome-wide scans and imputed data to the approximately 2.5 million single-nucleotide polymorphisms in HapMap. Within each study, Cox proportional hazards regression models provided age- and sex-adjusted estimates of the association between each variant and time to incident HF. Fixed-effect meta-analyses combined results for each single-nucleotide polymorphism from the 4 cohorts to produce an overall association estimate and P value. A genome-wide significance P value threshold was set a priori at 5.0x10(-7). During a mean follow-up of 11.5 years, 2526 incident HF events (12%) occurred in 20 926 European-ancestry participants. The meta-analysis identified a genome-wide significant locus at chromosomal position 15q22 (1.4x10(-8)), which was 58.8 kb from USP3. Among 2895 African-ancestry participants, 466 incident HF events (16%) occurred during a mean follow-up of 13.7 years. One genome-wide significant locus was identified at 12q14 (6.7x10(-8)), which was 6.3 kb from LRIG3. CONCLUSIONS: We identified 2 loci that were associated with incident HF and exceeded genome-wide significance. The findings merit replication in other community-based settings of incident HF. |
DOI | 10.1161/CIRCGENETICS.109.895763 |
Alternate Journal | Circ Cardiovasc Genet |
PubMed ID | 20445134 |
PubMed Central ID | PMC3025695 |
Grant List | N01 HC085086 / HC / NHLBI NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States N01 HC075150 / HC / NHLBI NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States N01 HC055015 / HC / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States N01 HC055016 / HC / NHLBI NIH HHS / United States N01HC55020 / HL / NHLBI NIH HHS / United States UL1RR025005 / RR / NCRR NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States N01 HC055022 / HC / NHLBI NIH HHS / United States U01 HL080295-04 / HL / NHLBI NIH HHS / United States N01 HC085081 / HC / NHLBI NIH HHS / United States R01HL077477 / HL / NHLBI NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States R01 HL087652-03 / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States R01 HL093328-01 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States N01 HC085083 / HC / NHLBI NIH HHS / United States N01 HC055018 / HC / NHLBI NIH HHS / United States N01 HC025195 / HC / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States R01 HL077477 / HL / NHLBI NIH HHS / United States N02 HL64278 / HL / NHLBI NIH HHS / United States N01 HC085085 / HC / NHLBI NIH HHS / United States R01 HL059367-10 / HL / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States HHSN268200625226C / / PHS HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States 2K24HL04334 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States K24 HL004334 / HL / NHLBI NIH HHS / United States N01 HC085082 / HC / NHLBI NIH HHS / United States N01 HC055019 / HC / NHLBI NIH HHS / United States R01 HL077477-01 / HL / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States N01 HC085080 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States M01RR00425 / RR / NCRR NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States N01 HC055222 / HC / NHLBI NIH HHS / United States R01 HL 087652 / HL / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States R01 HL086694-03 / HL / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States N01 HC055021 / HC / NHLBI NIH HHS / United States M01 RR000425 / RR / NCRR NIH HHS / United States K24 HL004334-08 / HL / NHLBI NIH HHS / United States N01 HC085084 / HC / NHLBI NIH HHS / United States UL1 RR025005-01 / RR / NCRR NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States R01 HL093328 / HL / NHLBI NIH HHS / United States P30 DK063491-04 / DK / NIDDK NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States R01 HL087641-01 / HL / NHLBI NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01 HC055020 / HC / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01 HC085079 / HC / NHLBI NIH HHS / United States M01 RR000425-30S1 / RR / NCRR NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States U01 HG004402-02 / HG / NHGRI NIH HHS / United States |