期刊
CIRCULATION-CARDIOVASCULAR GENETICS
卷 3, 期 3, 页码 256-U79出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCGENETICS.109.895763
关键词
epidemiology; genetics; heart failure; genome; wide variation; incidence
资金
- National Heart, Lung, and Blood Institute (NHLBI) [N01HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01HC- 55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694]
- National Human Genome Research Institute [U01HG004402]
- National Institutes of Health (NIH) [HHSN268200625226C]
- NIH, National Institutes of Environmental Health Sciences
- NHLBI [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL 087652, N01-HC25195, 2K24HL04334, R01HL077477, R01HL093328]
- National Center for Research Resources [M01RR00425]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]
- Affymetrix, Inc [N02-HL-6-4278]
- Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center
- NWO [175.010.2005.011, 911.03.012]
- Netherlands Genomics Initiative (NGI)/NWO [050-060-810]
- Netherlands Foundation for Scientific Research (NWO, VICI) [918-76-619]
- [UL1RR025005]
- DIVISION OF EPIDEMIOLOGY AND CLINICAL APPLICATIONS [N01HC085082, N01HC055016, N01HC025195, N01HC055021, N01HC015103, N01HC055022, N01HC085080, N01HC055222, N01HC075150, N01HC085083, N01HC085079, N01HC085085, N01HC055019, N01HC035129, N01HC055015, N01HC085081, N01HC045133, N01HC055020, N01HC055018, N01HC085084, N01HC085086] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR025005, M01RR000425] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [U01HL080295, R42HL055018, R01HL086694, R01HL087652, R41HL055019, R41HL055018, R01HL064278, R01HL093328, K24HL004334, ZIAHL006001, R01HL087641, R01HL059367] Funding Source: NIH RePORTER
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [U01HG004402] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK063491] Funding Source: NIH RePORTER
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.)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据