Genome-wide analysis of blood pressure variability and ischemic stroke.
Genome-wide analysis of blood pressure variability and ischemic stroke.
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DOI：
10.1161/strokeaha.113.002186
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发表时间：
2013-10
期刊：
影响因子：
8.3
通讯作者：
International Stroke Genetics Consortium
中科院分区：
文献类型：
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作者：
Yadav S;Cotlarciuc I;Munroe PB;Khan MS;Nalls MA;Bevan S;Cheng YC;Chen WM;Malik R;McCarthy NS;Holliday EG;Speed D;Hasan N;Pucek M;Rinne PE;Sever P;Stanton A;Shields DC;Maguire JM;McEvoy M;Scott RJ;Ferrucci L;Macleod MJ;Attia J;Markus HS;Sale MM;Worrall BB;Mitchell BD;Dichgans M;Sudlow C;Meschia JF;Rothwell PM;Caulfield M;Sharma P;International Stroke Genetics Consortium
访视间血压变异性与缺血性卒中相关。我们试图确定这种变异是否有遗传病因，以及与血压变异相关的遗传变异是否也与缺血性卒中相关。对来自盎格鲁-斯堪的纳维亚心脏结局试验（阿斯科特）研究的3,802名个体进行了影响血压变异性的基因座GWAS，其中可获得长期访视间和访视内血压测量。由于血压变异性与缺血性卒中密切相关，我们在一个独立的缺血性卒中人群（包括8，624例病例和12，722例对照）以及阿斯科特研究的3，900名额外（斯堪的纳维亚）参与者中对哨兵SNP进行基因分型，以复制我们的发现。阿斯科特发现GWAS在NLGN 1基因（3q26.31）内鉴定了一组与BP变异性相关的17个相关SNP。与rs 976683的关联最强（p=1.4×10−8）。对rs 976683的条件分析没有提供该位点额外独立关联的证据。在缺血性卒中患者中分析rs 976683与总体卒中无关联（OR 1.02; 95% CI 0.97-1.07; p=0.52）或其亚型：CE（OR 1.07; 95% CI 0.97-1.16; p=0.17）、LVD（OR 0.98; 95% CI 0.89-1.07; p=0.60）和SVD（OR 1.07; 95% CI 0.97-1.17; p=0.19）。在额外的（斯堪的纳维亚）阿斯科特参与者中，未发现rs 976683与BP变异性之间存在关联的证据（p=0.18）。我们在NLGN 1基因座上发现了一组SNP，这些SNP与BP变异性显着相关。后续分析并不支持与缺血性中风及其亚型的风险相关。
Visit-to-visit variability in BP is associated with ischemic stroke. We sought to determine whether such variability has a genetic aetiology and whether genetic variants associated with BP variability are also associated with ischemic stroke. A GWAS for loci influencing BP variability was undertaken in 3,802 individuals from the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT) study where long-term visit-to-visit and within visit BP measures were available. Since BP variability is strongly associated with ischemic stroke, we genotyped the sentinel SNP in an independent ischemic stroke population comprising of 8,624 cases and 12,722 controls and in 3,900 additional (Scandinavian) participants from the ASCOT study in order to replicate our findings. The ASCOT discovery GWAS identified a cluster of 17 correlated SNPs within the NLGN1 gene (3q26.31) associated with BP variability. The strongest association was with rs976683 (p=1.4×10−8). Conditional analysis on rs976683 provided no evidence of additional independent associations at the locus. Analysis of rs976683 in ischemic stroke patients found no association for overall stroke (OR 1.02; 95% CI 0.97-1.07; p=0.52) or its sub-types: CE (OR 1.07; 95% CI 0.97-1.16; p=0.17), LVD (OR 0.98; 95% 0.89-1.07; p=0.60) and SVD (OR 1.07; 95% CI 0.97-1.17; p=0.19). No evidence for association was found between rs976683 and BP variability in the additional (Scandinavian) ASCOT participants (p=0.18). We identified a cluster of SNPs at the NLGN1 locus showing significant association with BP variability. Follow up analyses did not support an association with risk of ischemic stroke and its subtypes.