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全基因组荟萃分析确定93个风险位点并实现静脉血栓栓塞的风险预测
作者:小柯机器人 发布时间:2023/1/29 12:14:02

近日,丹麦哥本哈根大学Jonas Ghouse等研究人员合作发现,全基因组荟萃分析确定了93个风险位点,并实现了相当于单基因形式的静脉血栓栓塞风险预测。相关论文于2023年1月19日在线发表在《自然—遗传学》杂志上。

研究人员报告了一项全基因组的静脉血栓栓塞(VTE)关联研究,其纳入来自六个队列的811901419671例对照样本。研究人员人员确定了93风险位点,其中62个以前未报道。许多已确定的风险位点位于编码凝血级联或血小板功能的蛋白质的基因上。VTE多基因风险评分(PRS)能够有效识别高风险和低风险个体。PRS分布前0.1%的个体VTE风险与F2中变异G20210A (c.*97G> a)和F5中变异p.R534Q的纯合子或复合杂合子携带者相似。研究人员还记录了在PRS分布中最低10%的F2和F5突变携带者的风险与一般人群相似。研究人员进一步表明,PRS改善了个体风险预测,超越了遗传和临床风险因素。研究人员人员以孟德尔随机化为主题,报道了静脉血栓和动脉血栓形成的临床危险因素的共同程度,并发现一些动脉血栓形成的危险因素与静脉血栓形成的风险方向一致(例如,体重指数和吸烟),而另一些则不一致(例如,收缩压和甘油三酯水平)。

附:英文原文

Title: Genome-wide meta-analysis identifies 93 risk loci and enables risk prediction equivalent to monogenic forms of venous thromboembolism

Author: Ghouse, Jonas, Tragante, Vinicius, Ahlberg, Gustav, Rand, Sren A., Jespersen, Jakob B., Leine, Eva Birgitte, Vissing, Christoffer Rasmus, Truds, Linea, Jonsdottir, Ingileif, Banasik, Karina, Brunak, Sren, Ostrowski, Sisse R., Pedersen, Ole B., Srensen, Erik, Erikstrup, Christian, Bruun, Mie Topholm, Nielsen, Kaspar Rene, Kber, Lars, Christensen, Alex H., Iversen, Kasper, Jones, David, Knowlton, Kirk U., Nadauld, Lincoln, Halldorsson, Gisli H., Ferkingstad, Egil, Olafsson, Isleifur, Gretarsdottir, Solveig, Onundarson, Pall T., Sulem, Patrick, Thorsteinsdottir, Unnur, Thorgeirsson, Gudmundur, Gudbjartsson, Daniel F., Stefansson, Kari, Holm, Hilma, Olesen, Morten Salling, Bundgaard, Henning

Issue&Volume: 2023-01-19

Abstract: We report a genome-wide association study of venous thromboembolism (VTE) incorporating 81,190cases and 1,419,671controls sampled from six cohorts. We identify 93risk loci, of which 62 are previously unreported. Many of the identified risk loci are at genes encoding proteins with functions converging on the coagulation cascade or platelet function. A VTE polygenic risk score (PRS) enabled effective identification of both high- and low-risk individuals. Individuals within the top 0.1% of PRS distribution had a VTE risk similar to homozygous or compound heterozygous carriers of the variants G20210A (c.*97G>A) in F2 and p.R534Q in F5. We also document that F2 and F5 mutation carriers in the bottom 10% of the PRS distribution had a risk similar to that of the general population. We further show that PRS improved individual risk prediction beyond that of genetic and clinical risk factors. We investigated the extent to which venous and arterial thrombosis share clinical risk factors using Mendelian randomization, finding that some risk factors for arterial thrombosis were directionally concordant with VTE risk (for example, body mass index and smoking) whereas others were discordant (for example, systolic blood pressure and triglyceride levels).

DOI: 10.1038/s41588-022-01286-7

Source: https://www.nature.com/articles/s41588-022-01286-7

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:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex

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