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.
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.
  
  
  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.
authors.affiliation: Cardiovascular Health Study: Department of Epidemiology, University of Washington, Seattle, WA 98105, USA. nlsmith@u.washington.edu
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Smith
authors.forename: Janine F
authors.initials: JF
authors.lastname: Felix
authors.forename: Alanna C
authors.initials: AC
authors.lastname: Morrison
authors.forename: Serkalem
authors.initials: S
authors.lastname: Demissie
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Glazer
authors.forename: Laura R
authors.initials: LR
authors.lastname: Loehr
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
authors.forename: Thomas
authors.initials: T
authors.lastname: Lumley
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Rosamond
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Bis
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.forename: Emelia
authors.initials: E
authors.lastname: Benjamin
authors.forename: Yurii S
authors.initials: YS
authors.lastname: Aulchenko
authors.forename: Talin
authors.initials: T
authors.lastname: Haritunians
authors.forename: David
authors.initials: D
authors.lastname: Couper
authors.forename: Joanne
authors.initials: J
authors.lastname: Murabito
authors.forename: Ying A
authors.initials: YA
authors.lastname: Wang
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Stricker
authors.forename: John S
authors.initials: JS
authors.lastname: Gottdiener
authors.forename: Patricia P
authors.initials: PP
authors.lastname: Chang
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Rice
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.forename: Ervin R
authors.initials: ER
authors.lastname: Fox
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: James T
authors.initials: JT
authors.lastname: Willerson
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Jacqueline C M
authors.initials: JC
authors.lastname: Witteman
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D010450:Endopeptidases / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D006333:Heart Failure / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D064570:Ubiquitin-Specific Proteases; D044465:White People / Q000235:genetics*
chemical_list: D010450:Endopeptidases; C579221:USP3 protein, human; D064570:Ubiquitin-Specific Proteases
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