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.
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.
Morrison
Alanna C
AC
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
Felix
Janine F
JF
Cupples
L Adrienne
LA
Glazer
Nicole L
NL
Loehr
Laura R
LR
Dehghan
Abbas
A
Demissie
Serkalem
S
Bis
Joshua C
JC
Rosamond
Wayne D
WD
Aulchenko
Yurii S
YS
Wang
Ying A
YA
Haritunians
Talin
T
Folsom
Aaron R
AR
Rivadeneira
Fernando
F
Benjamin
Emelia J
EJ
Lumley
Thomas
T
Couper
David
D
Stricker
Bruno H
BH
O'Donnell
Christopher J
CJ
Rice
Kenneth M
KM
Chang
Patricia P
PP
Hofman
Albert
A
Levy
Daniel
D
Rotter
Jerome I
JI
Fox
Ervin R
ER
Uitterlinden
Andre G
AG
Wang
Thomas J
TJ
Psaty
Bruce M
BM
Willerson
James T
JT
van Duijn
Cornelia M
CM
Boerwinkle
Eric
E
Witteman
Jacqueline C M
JC
Vasan
Ramachandran S
RS
Smith
Nicholas L
NL
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*
C552173:CMTM7 protein, human; D018925:Chemokines; D062792:MARVEL Domain-Containing Proteins; D008565:Membrane Proteins
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