Genome-Wide Association Study Identifies First Locus Associated with Susceptibility to Cerebral Venous Thrombosis.
Genome-Wide Association Study Identifies First Locus Associated with Susceptibility to Cerebral Venous Thrombosis.
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DOI：
10.1002/ana.26205
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发表时间：
2021-11
影响因子：
11.2
通讯作者：
Sharma P
中科院分区：
文献类型：
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作者：
Ken-Dror G;Cotlarciuc I;Martinelli I;Grandone E;Hiltunen S;Lindgren E;Margaglione M;Duchez VLC;Triquenot AB;Zedde M;Mancuso M;Ruigrok YM;Marjot T;Worrall B;Majersik JJ;Metso TM;Putaala J;Haapaniemi E;Zuurbier SM;Brouwer MC;Passamonti SM;Abbattista M;Bucciarelli P;Mitchell BD;Kittner SJ;Lemmens R;Jern C;Pappalardo E;Costa P;Colombi M;de Sousa DA;Rodrigues S;Canhão P;Tkach A;Santacroce R;Favuzzi G;Arauz A;Colaizzo D;Spengos K;Hodge A;Ditta R;Pezzini A;Debette S;Coutinho JM;Thijs V;Jood K;Pare G;Tatlisumak T;Ferro JM;Sharma P
脑静脉血栓形成(CVT)是一种不常见的中风形式，主要影响年轻人。虽然遗传因素被认为在这种脑血管疾病中发挥了作用，但其遗传病因尚不清楚。进行全基因组关联研究，以确定影响CVT易感性的遗传变异。在882名被诊断患有CVT的欧洲人和1205名种族匹配的对照受试者中进行了一项两阶段的全基因组研究，这些受试者被分为发现数据集和独立复制数据集。在整个病例对照队列中，我们确定了9q34.2区域内的37个SNP与高度显著的关联。关联最强的是rs8176645(联合P=9.15×10−24；OR=2.01，95%CI：1.76~2.31)。这一发现集的发现在一个独立的欧洲队列中得到了验证。合并估计OR=2.6 5(95%CI：2.2 1~3.2 0，P=2.0 0×10−16)。该区域内的SNP与ABO基因编码区处于强连锁不平衡(LD)状态。ABO血型测定采用rs8176746和rs8176645等位基因组合。A、B、AB血型个体发生脑血管意外的风险是O型个体的2.85倍(95%CI：2.32~3.52，P=2.00×10−16)。我们提出了第一个与CVT遗传易感性密切相关的染色体区域。这一区域使患CVT的可能性增加一倍以上，这是一种比之前发现的任何亲血栓遗传风险标记都更大的风险。已鉴定的变异与ABO基因编码区处于强LD，但血型患病率不同，这为CVT的病理生理学提供了重要的新见解。
Cerebral venous thrombosis (CVT) is an uncommon form of stroke affecting mostly young individuals. Although genetic factors are thought to play a role in this cerebrovascular condition, its genetic etiology is not well understood. Genome-wide association study performed to identify genetic variants influencing susceptibility to CVT. A two-stage genome-wide study was undertaken in 882 Europeans diagnosed with CVT and 1205 ethnicity-matched control subjects divided into discovery and independent replication datasets. In the overall case-control cohort, we identified highly significant associations with 37 SNPs within 9q34.2 region. The strongest association was with rs8176645 (combined P=9.15×10−24; OR=2.01, 95%CI: 1.76–2.31). The discovery set findings were validated across an independent European cohort. Genetic risk score for this 9q34.2 region increases CVT risk by a pooled estimate OR=2.65 (95%CI: 2.21–3.20, P=2.00×10−16). SNPs within this region were in strong linkage disequilibrium (LD) with coding regions of the ABO gene. ABO blood group was determined using allele combination of SNPs rs8176746 and rs8176645. Blood groups A, B or AB, were at 2.85 times (95%CI: 2.32–3.52, P=2.00×10−16) increased risk of CVT compared with individuals with blood group-O. We present the first chromosomal region to robustly associate with a genetic susceptibility to CVT. This region more than doubles the likelihood of CVT, a risk greater than any previously identified thrombophilia genetic risk marker. That the identified variant is in strong LD with the coding region of the ABO gene with differences in blood group prevalence provides important new insights into the pathophysiology of CVT.
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影响因子：
14.8
作者：
通讯作者：
--
影响因子：
4.5
作者：
Melzer D;Perry JR;Hernandez D;Corsi AM;Stevens K;Rafferty I;Lauretani F;Murray A;Gibbs JR;Paolisso G;Rafiq S;Simon-Sanchez J;Lango H;Scholz S;Weedon MN;Arepalli S;Rice N;Washecka N;Hurst A;Britton A;Henley W;van de Leemput J;Li R;Newman AB;Tranah G;Harris T;Panicker V;Dayan C;Bennett A;McCarthy MI;Ruokonen A;Jarvelin MR;Guralnik J;Bandinelli S;Frayling TM;Singleton A;Ferrucci L
通讯作者：
Ferrucci L
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
DOI：
10.1161/atvbaha.119.313658
发表时间：
2020-03-01
影响因子：
8.7
作者：
Groot, Hilde E.;Sierra, Laura E. Villegas;van der Harst, Pim
通讯作者：
van der Harst, Pim