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.
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.
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DOI：
10.1161/circgenetics.109.895995
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发表时间：
2010-06
期刊：
影响因子：
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通讯作者：
Smith NL
中科院分区：
文献类型：
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作者：
Morrison AC;Felix JF;Cupples LA;Glazer NL;Loehr LR;Dehghan A;Demissie S;Bis JC;Rosamond WD;Aulchenko YS;Wang YA;Haritunians T;Folsom AR;Rivadeneira F;Benjamin EJ;Lumley T;Couper D;Stricker BH;O'Donnell CJ;Rice KM;Chang PP;Hofman A;Levy D;Rotter JI;Fox ER;Uitterlinden AG;Wang TJ;Psaty BM;Willerson JT;van Duijn CM;Boerwinkle E;Witteman JC;Vasan RS;Smith NL
预后和生存是心力衰竭 (HF) 患者的重要关注点。为了更好地了解心力衰竭预后的病理生理学，我们对来自四个基于社区的前瞻性队列的心力衰竭患者的 2,366,858 个单核苷酸多态性 (SNP) 与全因死亡率之间的关联进行了评估：社区动脉粥样硬化风险研究、心血管健康研究、弗雷明汉心脏研究和鹿特丹研究。参与者包括 2,526 名欧洲血统个体和 466 名非洲血统个体，他们在各自队列的随访期间遭遇了突发心力衰竭事件。在每项研究中，心力衰竭患者的遗传变异与死亡时间之间的关联均通过 Cox 比例风险模型进行评估，其中包括对心力衰竭事件发生时的性别和年龄进行调整。对四个欧洲血统研究人群（N = 1,645 例死亡）和两个非洲血统研究人群（N = 281 例死亡）进行了前瞻性固定效应荟萃分析。全基因组显着性设定为 P=5.0×10-7。对欧洲血统个体的荟萃分析发现，染色体 3p22 上的 CKLF 样 MARVEL 跨膜结构域内含子中存在一个全基因组显着位点，其中包含 7 个跨膜结构域（CMTM7，p = 3.2×10-7）。通过高信号 SNP (p < 1.0×10-5) 鉴定了欧洲血统个体中的另外 8 个基因座和非洲血统个体中的 4 个基因座，但不符合全基因组显着性。这项研究发现了一个与欧洲血统心力衰竭患者全因死亡率相关的新位点。这一发现值得进一步研究，包括在其他心力衰竭研究中进行复制。
Prognosis and survival are significant concerns for individuals with heart failure (HF). In order 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 four community-based prospective cohorts: the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. Participants were 2,526 individuals of European ancestry and 466 individuals of African ancestry who suffered 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 four study populations of European ancestry (N=1,645 deaths) and for the two populations of African ancestry (N=281 deaths). Genome-wide significance was set at P=5.0×10-7. Meta-analytic findings among individuals of European ancestry revealed one genome-wide significant locus on chromosome 3p22 in an intron of CKLF-like MARVEL transmembrane domain containing 7 (CMTM7, p = 3.2×10-7). Eight additional loci in individuals of European ancestry and four loci in individuals of African ancestry were identified by high-signal SNPs (p < 1.0×10-5), but did not meet genome-wide significance. 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.