当前位置:科学网首页 > 小柯机器人 >详情
全基因组关联分析揭示颅内动脉瘤的风险位点
作者:小柯机器人 发布时间:2020/11/17 16:10:02

荷兰乌得勒支大学Ynte M. Ruigrok、Mark K. Bakker究组近日取得一项新成果。经过不懈努力,他们通过对颅内动脉瘤的全基因组关联分析确定了17个风险位点和与临床危害相关遗传因素。这一研究成果发表在2020年11月16日的《自然-遗传学》上。

为了发现新的风险基因座和颅内动脉瘤的遗传结构,研究人员在10754例欧洲谱系和306882例东亚谱系的对照研究中进行了跨谱系的全基因组关联分析。研究发现了17个风险基因座,其中11个是之前未知的。研究人员揭示了一种多基因架构,其解释了超过一半疾病的遗传特点。研究发现破裂和未破裂颅内动脉瘤之间存在高度的遗传相关性。通过使用基因作图和遗传特征富集研究人员还发现了内皮细胞的潜在功能。靶向药物富集显示颅内动脉瘤与抗癫痫药和性激素药物之间的多效性,这为了解颅内动脉瘤的病理生理学提供了见解。

最后,吸烟和高血压是两个主要的临床风险因素,它们在颅内动脉瘤发病中起重要作用,并造成了颅内动脉瘤与其他脑血管疾病之间大部分的遗传相关性。

据介绍,颅内动脉瘤破裂会导致蛛网膜下腔出血,这是造成严重中风的原因。

附:英文原文

Title: Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors

Author: Mark K. Bakker, Rick A. A. van der Spek, Wouter van Rheenen, Sandrine Morel, Romain Bourcier, Isabel C. Hostettler, Varinder S. Alg, Kristel R. van Eijk, Masaru Koido, Masato Akiyama, Chikashi Terao, Koichi Matsuda, Robin G. Walters, Kuang Lin, Liming Li, Iona Y. Millwood, Zhengming Chen, Guy A. Rouleau, Sirui Zhou, Kristiina Rannikme, Cathie L. M. Sudlow, Henry Houlden, Leonard H. van den Berg, Christian Dina, Olivier Naggara, Jean-Christophe Gentric, Eimad Shotar, Franois Eugne, Hubert Desal, Bendik S. Winsvold, Sigrid Brte, Marianne Bakke Johnsen, Ben M. Brumpton, Marie Sfteland Sandvei, Cristen J. Willer, Kristian Hveem, John-Anker Zwart, W. M. Monique Verschuren, Christoph M. Friedrich, Sven Hirsch, Sabine Schilling, Jrme Dauvillier, Olivier Martin, Gregory T. Jones, Matthew J. Bown, Nerissa U. Ko, Helen Kim, Jonathan R. I. Coleman, Gerome Breen, Jonathan G. Zaroff, Catharina J. M. Klijn, Rainer Malik, Martin Dichgans, Muralidharan Sargurupremraj, Turgut Tatlisumak, Philippe Amouyel, Stphanie Debette, Gabriel J. E. Rinkel, Bradford B. Worrall

Issue&Volume: 2020-11-16

Abstract: Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits. Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.

DOI: 10.1038/s41588-020-00725-7

Source: https://www.nature.com/articles/s41588-020-00725-7

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