Association of Genome-Wide Variation With the Risk of Incident Heart Failure in Adults of European and African Ancestry
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Published:2010-06
Issue:3
Volume:3
Page:256-266
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ISSN:1942-325X
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Container-title:Circulation: Cardiovascular Genetics
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language:en
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Short-container-title:Circ Cardiovasc Genet
Author:
Smith Nicholas L.1, Felix Janine F.1, Morrison Alanna C.1, Demissie Serkalem1, Glazer Nicole L.1, Loehr Laura R.1, Cupples L. Adrienne1, Dehghan Abbas1, Lumley Thomas1, Rosamond Wayne D.1, Lieb Wolfgang1, Rivadeneira Fernando1, Bis Joshua C.1, Folsom Aaron R.1, Benjamin Emelia1, Aulchenko Yurii S.1, Haritunians Talin1, Couper David1, Murabito Joanne1, Wang Ying A.1, Stricker Bruno H.1, Gottdiener John S.1, Chang Patricia P.1, Wang Thomas J.1, Rice Kenneth M.1, Hofman Albert1, Heckbert Susan R.1, Fox Ervin R.1, O'Donnell Christopher J.1, Uitterlinden Andre G.1, Rotter Jerome I.1, Willerson James T.1, Levy Daniel1, van Duijn Cornelia M.1, Psaty Bruce M.1, Witteman Jacqueline C.M.1, Boerwinkle Eric1, Vasan Ramachandran S.1
Affiliation:
1. From the Cardiovascular Health Study: Departments of Epidemiology (N.L.S., S.R.H., B.M.P.), Medicine (N.L.G., J.C.B., B.M.P.), Biostatistics (T.L., K.M.R.), and Health Services (B.M.P.) University of Washington, Seattle, Wash.; Seattle Epidemiologic Research and Information Center of the Department of Veterans Affairs Office of Research and Development (N.L.S.), Seattle, Wash.; Group Health Research Institute (S.R.H., B.M.P., N.L.S.) Group Health, Seattle, Wash.; and Department of Cardiology (J.S.G....
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 ≈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 5.0×10
−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 (1.4×10
−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 (6.7×10
−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.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Genetics(clinical),Cardiology and Cardiovascular Medicine,Genetics
Cited by
178 articles.
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