title: 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.
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.
  
  
  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.
authors.affiliation: Atherosclerosis Risk in Communities Study: University of Texas Health Science Center at Houston, Human Genetics Center, Houston, TX 77030, USA. Alanna.C.Morrison@uth.tmc.edu
authors.forename: Alanna C
authors.initials: AC
authors.lastname: Morrison
authors.forename: Janine F
authors.initials: JF
authors.lastname: Felix
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Glazer
authors.forename: Laura R
authors.initials: LR
authors.lastname: Loehr
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
authors.forename: Serkalem
authors.initials: S
authors.lastname: Demissie
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Bis
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Rosamond
authors.forename: Yurii S
authors.initials: YS
authors.lastname: Aulchenko
authors.forename: Ying A
authors.initials: YA
authors.lastname: Wang
authors.forename: Talin
authors.initials: T
authors.lastname: Haritunians
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: Thomas
authors.initials: T
authors.lastname: Lumley
authors.forename: David
authors.initials: D
authors.lastname: Couper
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Stricker
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Rice
authors.forename: Patricia P
authors.initials: PP
authors.lastname: Chang
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Ervin R
authors.initials: ER
authors.lastname: Fox
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: James T
authors.initials: JT
authors.lastname: Willerson
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Jacqueline C M
authors.initials: JC
authors.lastname: Witteman
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Smith
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D018925:Chemokines / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006333:Heart Failure / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D007438:Introns; D062792:MARVEL Domain-Containing Proteins; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics*
chemical_list: C552173:CMTM7 protein, human; D018925:Chemokines; D062792:MARVEL Domain-Containing Proteins; D008565:Membrane Proteins
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