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.
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.
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DOI：
10.1161/circgenetics.109.895763
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发表时间：
2010-06
期刊：
影响因子：
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通讯作者：
Vasan RS
中科院分区：
文献类型：
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作者：
Smith NL;Felix JF;Morrison AC;Demissie S;Glazer NL;Loehr LR;Cupples LA;Dehghan A;Lumley T;Rosamond WD;Lieb W;Rivadeneira F;Bis JC;Folsom AR;Benjamin E;Aulchenko YS;Haritunians T;Couper D;Murabito J;Wang YA;Stricker BH;Gottdiener JS;Chang PP;Wang TJ;Rice KM;Hofman A;Heckbert SR;Fox ER;O'Donnell CJ;Uitterlinden AG;Rotter JI;Willerson JT;Levy D;van Duijn CM;Psaty BM;Witteman JC;Boerwinkle E;Vasan RS
尽管遗传因素会导致心力衰竭（HF）的发生，但迄今为止还没有关于HF风险的大规模全基因组调查发表。我们通过荟萃分析来自4个社区前瞻性队列的数据，研究了2,478,304个单核苷酸多态性（snp）与心衰事件的关系：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。这些分析的合格参与者为欧洲或非洲血统，基线时无临床HF。每项研究都独立进行了全基因组扫描，并将数据输入到HapMap中的约250万个snp中。在每项研究中，Cox比例风险回归模型提供了年龄和性别调整后的每种变异与HF发生时间之间的关联估计。固定效应荟萃分析将4个队列中每个SNP的结果结合起来，得出总体关联估计和p值。全基因组显著性p值阈值先验设置为5.0×10−7。在平均11.5年的随访期间，20,926名欧洲血统参与者中发生了2,526例心衰事件（12%）。meta分析在染色体位置15q22 （1.4×10−8）发现了一个全基因组显著位点，该位点距离USP3 58.8 kb。在2,895名非洲裔参与者中，在平均13.7年的随访期间发生了466例心衰事件（16%）。在12q14 （6.7×10−8）处发现了一个全基因组显著位点，距离LRIG3 6.3 kb。我们确定了2个与心衰事件相关的位点，并且超过了全基因组意义。研究结果值得在其他社区的心衰事件中复制。
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 investigated the association of 2,478,304 single nucleotide polymorphisms (SNPs) 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. 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 SNPs 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 SNP 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, 2,526 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 2,895 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. 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.