Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium: Design of prospective meta-analyses of genome-wide association studies from 5 cohorts.
Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium: Design of prospective meta-analyses of genome-wide association studies from 5 cohorts.
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DOI：
10.1161/circgenetics.108.829747
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发表时间：
2009-02
期刊：
影响因子：
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通讯作者：
CHARGE Consortium
中科院分区：
文献类型：
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作者：
Psaty BM;O'Donnell CJ;Gudnason V;Lunetta KL;Folsom AR;Rotter JI;Uitterlinden AG;Harris TB;Witteman JC;Boerwinkle E;CHARGE Consortium
背景-全基因组关联研究的主要目的是确定与个体间危险因素水平、亚临床疾病程度或临床疾病风险相关的新的遗传位点。对大样本量的要求和复制的重要性已经成为科学合作的强大激励因素。方法-基因组流行病学联盟中的心脏和衰老研究队列的形成是为了促进全基因组关联研究荟萃分析和多个大型人群队列研究之间的复制机会，其以标准化的方式收集数据并代表用于估计疾病发病率的优选方法。基因组流行病学联盟心脏和衰老研究队列的设计包括来自美国和欧洲的5项前瞻性队列研究：年龄、基因/环境易感性-雷克雅未克研究、社区动脉粥样硬化风险研究、心血管健康研究、心脏病研究和鹿特丹研究。这些队列研究共涉及约38000名个体的全基因组数据，以类似的方式测量了大量与健康相关的表型。对于每个协调的性状，通过荟萃分析结合队列内全基因组关联研究分析。一个前瞻性的荟萃分析的数据，从所有5个队列，与适当选择的水平的全基因组的统计学意义，是一个强大的方法来寻找真正的表型协会与新的遗传locos.Conclusions-The队列心脏和衰老研究基因组流行病学联盟和合作非成员研究或联盟提供了一个很好的框架，为识别的遗传决定因素的风险因素，亚临床疾病指标和临床事件。
Background—The primary aim of genome-wide association studies is to identify novel genetic loci associated with interindividual variation in the levels of risk factors, the degree of subclinical disease, or the risk of clinical disease. The requirement for large sample sizes and the importance of replication have served as powerful incentives for scientific collaboration.Methods—The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium was formed to facilitate genome-wide association studies meta-analyses and replication opportunities among multiple large population-based cohort studies, which collect data in a standardized fashion and represent the preferred method for estimating disease incidence. The design of the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium includes 5 prospective cohort studies from the United States and Europe: the Age, Gene/Environment Susceptibility—Reykjavik Study, the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. With genome-wide data on a total of about 38 000 individuals, these cohort studies have a large number of health-related phenotypes measured in similar ways. For each harmonized trait, within-cohort genome-wide association study analyses are combined by meta-analysis. A prospective meta-analysis of data from all 5 cohorts, with a properly selected level of genome-wide statistical significance, is a powerful approach to finding genuine phenotypic associations with novel genetic loci.Conclusions—The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and collaborating non-member studies or consortia provide an excellent framework for the identification of the genetic determinants of risk factors, subclinical-disease measures, and clinical events.