TY - JOUR
T1 - 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
AU - Smith, NL
AU - Felix, Janine
AU - Morrison, AC
AU - Demissie, S
AU - Glazer, NL
AU - Loehr, LR
AU - Cupples, LA
AU - Dehghan, Abbas
AU - Lumley, T
AU - Rosamond, WD
AU - Lieb, W
AU - Rivadeneira, Fernando
AU - Bis, JC
AU - Folsom, AR
AU - Benjamin, E
AU - Aulchenko, YS
AU - Haritunians, T
AU - Couper, D
AU - Murabito, J
AU - Wang, YA
AU - Stricker, Bruno
AU - Gottdiener, JS
AU - Chang, PP
AU - Wang, TJ
AU - Rice, KM
AU - Hofman, Bert
AU - Heckbert, SR
AU - Fox, ER
AU - O'Donnell, CJ
AU - Uitterlinden, André
AU - Rotter, JI
AU - Willerson, JT
AU - Levy, D
AU - Duijn, Cornelia
AU - Psaty, BM
AU - Witteman, JCM
AU - Boerwinkle, E
AU - Vasan, RS
PY - 2010
Y1 - 2010
N2 - 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 approximate to 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 x 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 x 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 x 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. (Circ Cardiovasc Genet. 2010;3:256-266.)
AB - 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 approximate to 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 x 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 x 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 x 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. (Circ Cardiovasc Genet. 2010;3:256-266.)
U2 - 10.1161/CIRCGENETICS.109.895763
DO - 10.1161/CIRCGENETICS.109.895763
M3 - Article
C2 - 20445134
SN - 1942-325X
VL - 3
SP - 256-U79
JO - Circulation-cardiovascular genetics
JF - Circulation-cardiovascular genetics
IS - 3
ER -