PDF(Pubmed)
Abstract：
UNASSIGNED: Platelet indices (PIs) are hematological parameters that indicate the number, morphology, and activation of platelets. Although some clinical trials suggest an association between PIs and the risk of stroke, the lack of robust evidence is attributed to confounding effects and reverse causation.
UNASSIGNED: This study aimed to evaluate the association between PIs and stroke risk through Mendelian randomization (MR) while exploring the mediating effect of blood pressure in this association.
UNASSIGNED: We identified genetic variants associated with PIs, including platelet count (PLT), platelet distribution width (PDW), mean platelet volume (MPV), and platelet crit (PCT), in the UK Biobank (n = 350,474). Relevant genome-wide association studies were utilized to gather summary statistics pertaining to the traits of interest. We primarily used the inverse-variance weighted analysis to obtain estimates for individual causal power.
UNASSIGNED: We observed a positive correlation between genetically predicted increases in PCT levels with the stroke onset [PCT: OR (95%CI) = 1.113(1.047, 1.183), p < 0.001]. However, no significant causal relationship was found between PLT, PDW, and MPV and the risk of stroke [PLT: OR (95%CI) = 1.037(0.979, 1.098), p = 0.221; PDW: OR (95%CI) = 0.973(0.923, 1.024), p = 0.294; MPV: OR (95%CI) = 0.990(0.945, 1.038), p = 0.675]. Multivariable MR analyses and mediation analysis found that the proportion mediated by systolic blood pressure (SBP) is 23.71% [95%CI (10.85-33.31%)] and the proportion mediated by diastolic blood pressure (DBP) is 28.09% [95%CI (12.92-39.63%)].
UNASSIGNED: This large MR study presents evidence for the potential causal relationship between the PCT level and the risk of ischemic stroke, which might be mediated by blood pressure.
UNASSIGNED: This study aimed to evaluate the association between PIs and stroke risk through Mendelian randomization (MR) while exploring the mediating effect of blood pressure in this association.
UNASSIGNED: We identified genetic variants associated with PIs, including platelet count (PLT), platelet distribution width (PDW), mean platelet volume (MPV), and platelet crit (PCT), in the UK Biobank (n = 350,474). Relevant genome-wide association studies were utilized to gather summary statistics pertaining to the traits of interest. We primarily used the inverse-variance weighted analysis to obtain estimates for individual causal power.
UNASSIGNED: We observed a positive correlation between genetically predicted increases in PCT levels with the stroke onset [PCT: OR (95%CI) = 1.113(1.047, 1.183), p < 0.001]. However, no significant causal relationship was found between PLT, PDW, and MPV and the risk of stroke [PLT: OR (95%CI) = 1.037(0.979, 1.098), p = 0.221; PDW: OR (95%CI) = 0.973(0.923, 1.024), p = 0.294; MPV: OR (95%CI) = 0.990(0.945, 1.038), p = 0.675]. Multivariable MR analyses and mediation analysis found that the proportion mediated by systolic blood pressure (SBP) is 23.71% [95%CI (10.85-33.31%)] and the proportion mediated by diastolic blood pressure (DBP) is 28.09% [95%CI (12.92-39.63%)].
UNASSIGNED: This large MR study presents evidence for the potential causal relationship between the PCT level and the risk of ischemic stroke, which might be mediated by blood pressure.
摘要：
■血小板指数（PI）是指示数字的血液学参数，形态学,和血小板的活化。尽管一些临床试验表明PI与卒中风险之间存在关联，缺乏确凿的证据归因于混杂效应和反向因果关系.
■本研究旨在通过孟德尔随机化（MR）评估PI与卒中风险之间的关联，同时探索血压在这种关联中的中介作用。
■我们确定了与PI相关的遗传变异，包括血小板计数（PLT），血小板分布宽度（PDW），平均血小板体积（MPV），和血小板暴动(PCT)，在英国生物库(n=350,474)。利用相关的全基因组关联研究来收集与感兴趣的性状有关的汇总统计数据。我们主要使用逆方差加权分析来获得个体因果力的估计。
■我们观察到基因预测的PCT水平增加与卒中发作之间呈正相关[PCT:OR(95CI)=1.113(1.047,1.183)，p<0.001]。然而,PLT之间没有发现显著的因果关系，PDW,MPV和卒中风险[PLT：OR（95CI）=1.037（0.979，1.098），p=0.221；PDW：OR（95CI）=0.973（0.923，1.024），p=0.294；MPV：OR（95CI）=0.990（0.945，1.038），p=0.675]。多变量MR分析和中介分析发现，收缩压（SBP）介导的比例为23.71％[95CI（10.85-33.31％）]，舒张压（DBP）介导的比例为28.09％[95CI（12.92-39.63％）]。
■这项大型MR研究提供了PCT水平与缺血性卒中风险之间潜在因果关系的证据。这可能是由血压介导的。
■本研究旨在通过孟德尔随机化（MR）评估PI与卒中风险之间的关联，同时探索血压在这种关联中的中介作用。
■我们确定了与PI相关的遗传变异，包括血小板计数（PLT），血小板分布宽度（PDW），平均血小板体积（MPV），和血小板暴动(PCT)，在英国生物库(n=350,474)。利用相关的全基因组关联研究来收集与感兴趣的性状有关的汇总统计数据。我们主要使用逆方差加权分析来获得个体因果力的估计。
■我们观察到基因预测的PCT水平增加与卒中发作之间呈正相关[PCT:OR(95CI)=1.113(1.047,1.183)，p<0.001]。然而,PLT之间没有发现显著的因果关系，PDW,MPV和卒中风险[PLT：OR（95CI）=1.037（0.979，1.098），p=0.221；PDW：OR（95CI）=0.973（0.923，1.024），p=0.294；MPV：OR（95CI）=0.990（0.945，1.038），p=0.675]。多变量MR分析和中介分析发现，收缩压（SBP）介导的比例为23.71％[95CI（10.85-33.31％）]，舒张压（DBP）介导的比例为28.09％[95CI（12.92-39.63％）]。
■这项大型MR研究提供了PCT水平与缺血性卒中风险之间潜在因果关系的证据。这可能是由血压介导的。
