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心脏代谢特征的人群基因组学:伦敦大学学院-伦敦卫生与热带医学院-爱丁堡大学-布里斯托大学(UCLEB)联盟的设计。

Population genomics of cardiometabolic traits: design of the University College London-London School of Hygiene and Tropical Medicine-Edinburgh-Bristol (UCLEB) Consortium.

机构信息

Department of Epidemiology & Public Health, UCL Institute of Epidemiology & Health Care, University College London, London, United Kingdom.

出版信息

PLoS One. 2013 Aug 20;8(8):e71345. doi: 10.1371/journal.pone.0071345. eCollection 2013.

Abstract

Substantial advances have been made in identifying common genetic variants influencing cardiometabolic traits and disease outcomes through genome wide association studies. Nevertheless, gaps in knowledge remain and new questions have arisen regarding the population relevance, mechanisms, and applications for healthcare. Using a new high-resolution custom single nucleotide polymorphism (SNP) array (Metabochip) incorporating dense coverage of genomic regions linked to cardiometabolic disease, the University College-London School-Edinburgh-Bristol (UCLEB) consortium of highly-phenotyped population-based prospective studies, aims to: (1) fine map functionally relevant SNPs; (2) precisely estimate individual absolute and population attributable risks based on individual SNPs and their combination; (3) investigate mechanisms leading to altered risk factor profiles and CVD events; and (4) use Mendelian randomisation to undertake studies of the causal role in CVD of a range of cardiovascular biomarkers to inform public health policy and help develop new preventative therapies.

摘要

通过全基因组关联研究,在确定影响心脏代谢特征和疾病结果的常见遗传变异方面已经取得了重大进展。然而,知识仍然存在差距,并且关于人口相关性、机制和医疗保健应用的新问题已经出现。使用一种新的高分辨率定制单核苷酸多态性 (SNP) 阵列(Metabochip),该阵列包含与心脏代谢疾病相关的基因组区域的密集覆盖,伦敦大学学院-爱丁堡大学-布里斯托大学 (UCLEB) 联盟的高度表型基于人群的前瞻性研究旨在:(1) 精细映射功能相关的 SNP;(2) 基于个体 SNP 及其组合,精确估计个体绝对风险和人群归因风险;(3) 研究导致危险因素谱和 CVD 事件改变的机制;(4) 使用孟德尔随机化研究一系列心血管生物标志物在 CVD 中的因果作用,为公共卫生政策提供信息,并帮助开发新的预防疗法。

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