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大规模研究揭示静脉血栓栓塞风险相关基因座
作者:小柯机器人 发布时间:2019/11/2 23:46:35

美国哈佛医学院Pradeep Natarajan等研究人员利用静脉血栓栓塞的全基因组关联分析,确定了新的风险基因座以及与动脉血管疾病之间的遗传重叠。该研究成果于2019年11月1日,在线发表于国际学术期刊《自然—遗传学》。

研究人员在"百万老兵计划"和英国生物银行中进行了一项全基因组关联研究,测试了约1300万个与静脉血栓栓塞相关的DNA序列变异(26066例和624,053个对照),并对这两项研究进行了荟萃分析,然后进行独立复制多达17672例静脉血栓栓塞病例和167295例对照。研究人员确定了22个以前未知的基因座,使与静脉血栓栓塞相关的基因座总数达到了33个,并随后对其进行精细映射。研究人员为静脉血栓栓塞症建立了全基因组多基因风险评分,其可确定与建立的因子V Leiden p.R506Q和凝血酶原G20210A突变的携带者同等的静脉血栓栓塞风险。这些数据为静脉血栓栓塞的遗传流行病学提供了机制见解,并提示静脉和动脉性心血管疾病之间的重叠比以前想象的要大。

据悉,静脉血栓栓塞是导致死亡的重要原因,但其遗传决定因素尚未完全确定。

附:英文原文
 
Title:Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease
 
Author:Derek Klarin, Emma Busenkell, Renae Judy, Julie Lynch, Michael Levin, Jeffery Haessler, Krishna Aragam, Mark Chaffin, Mary Haas, Sara Lindström, Themistocles L. Assimes, Jie Huang, Kyung Min Lee, Qing Shao, Jennifer E. Huffman, Christopher Kabrhel, Yunfeng Huang, Yan V. Sun, Marijana Vujkovic, Danish Saleheen, Donald R. Miller, Peter Reaven, Scott DuVall, William E. Boden, Saiju Pyarajan, Alex P. Reiner, David-Alexandre Trégouët, Peter Henke, Charles Kooperberg, J. Michael Gaziano, John Concato, Daniel J. Rader, Kelly Cho, Kyong-Mi Chang, Peter W. F. Wilson, Nicholas L. Smith, Christopher J. O’Donnell, Philip S. Tsao, Sekar Kathiresan, Andrea Obi, Scott M. Damrauer, Pradeep Natarajan, INVENT Consortium & Veterans Affairs’ Million Veteran Program
 
Issue&Volume:01 November 2019
 
Abstract: Venous thromboembolism is a significant cause of mortality1, yet its genetic determinants are incompletely defined. We performed a discovery genome-wide association study in the Million Veteran Program and UK Biobank, with testing of approximately 13 million DNA sequence variants for association with venous thromboembolism (26,066 cases and 624,053 controls) and meta-analyzed both studies, followed by independent replication with up to 17,672 venous thromboembolism cases and 167,295 controls. We identified 22 previously unknown loci, bringing the total number of venous thromboembolism-associated loci to 33, and subsequently fine-mapped these associations. We developed a genome-wide polygenic risk score for venous thromboembolism that identifies 5% of the population at an equivalent incident venous thromboembolism risk to carriers of the established factor V Leiden p.R506Q and prothrombin G20210A mutations. Our data provide mechanistic insights into the genetic epidemiology of venous thromboembolism and suggest a greater overlap among venous and arterial cardiovascular disease than previously thought.
 
DOI:10.1038/s41588-019-0519-3
 
Source: https://www.nature.com/articles/s41588-019-0519-3

期刊信息

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex