期刊
CIRCULATION-CARDIOVASCULAR GENETICS
卷 3, 期 3, 页码 248-U64出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCGENETICS.109.895995
关键词
heart failure; all-cause mortality; genetics; genome-wide variation; mortality
资金
- National Heart, Lung, and Blood Institute [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, R01HL086694]
- National Human Genome Research Institute [U01HG004402]
- National Institutes of Health [HHSN268200625226C]
- National Institutes of Health, National Institutes of Environmental Health Sciences
- National Heart Lung and Blood Institute [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295, R01 HL 087652, N01-HC-25195]
- National Center for Research Resources [M01RR00425-39]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]
- National Heart Lung Blood Institute [2K24HL04334, R01HL077477, R01HL093328]
- Erasmus Medical Center
- Erasmus University Rotterdam
- Netherlands Organization for Scientific Research
- Netherlands Organization for Health Research and Development
- Research Institute for Diseases in the Elderly
- Netherlands Heart Foundation
- Ministry of Health, Welfare and Sports
- Ministry of Education, Culture and Science
- European Commission
- Municipality of Rotterdam
- Netherlands Organization for Scientific Research (NWO) [918-76-619]
- Netherlands Organization for Scientific Research [175.010.2005.011, 911.03.012]
- Research Institute for Diseases
- Netherlands Genomics Initiative/Netherlands Organization for Scientific Research [050-60-810]
- [UL1RR025005]
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. Methods and 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. (Circ Cardiovasc Genet. 2010;3:248-255.)
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