孟德尔随机化
医学
心脏病学
血压
内科学
抗高血压药
冲程(发动机)
全基因组关联研究
舒张期
单核苷酸多态性
遗传变异
遗传学
生物
基因
工程类
基因型
机械工程
作者
Marios K. Georgakis,Dipender Gill,Alastair Webb,Εvangelos Εvangelou,Paul Elliott,Cathie Sudlow,Abbas Dehghan,Rainer Malik,Ioanna Tzoulaki,Martin Dichgans
出处
期刊:Neurology
[Ovid Technologies (Wolters Kluwer)]
日期:2020-07-28
卷期号:95 (4)
被引量:58
标识
DOI:10.1212/wnl.0000000000009814
摘要
We employed Mendelian randomization to explore whether the effects of blood pressure (BP) and BP-lowering through different antihypertensive drug classes on stroke risk vary by stroke etiology.We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drug targets from genome-wide association studies (GWAS) on 757,601 individuals. Applying 2-sample Mendelian randomization, we examined associations with any stroke (67,162 cases; 454,450 controls), ischemic stroke and its subtypes (large artery, cardioembolic, small vessel stroke), intracerebral hemorrhage (ICH, deep and lobar), and the related small vessel disease phenotype of white matter hyperintensities (WMH).Genetic predisposition to higher systolic and diastolic BP was associated with higher risk of any stroke, ischemic stroke, and ICH. We found associations between genetically determined BP and all ischemic stroke subtypes with a higher risk of large artery and small vessel stroke compared to cardioembolic stroke, as well as associations with deep, but not lobar ICH. Genetic proxies for calcium channel blockers, but not β-blockers, were associated with lower risk of any stroke and ischemic stroke. Proxies for calcium channel blockers showed particularly strong associations with small vessel stroke and the related radiologic phenotype of WMH.This study supports a causal role of hypertension in all major stroke subtypes except lobar ICH. We find differences in the effects of BP and BP-lowering through antihypertensive drug classes between stroke subtypes and identify calcium channel blockade as a promising strategy for preventing manifestations of cerebral small vessel disease.
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