■虽然观察性研究证明了吸烟之间的联系,酒精消费,动脉僵硬度,由于潜在的混杂因素,建立因果关系已被证明具有挑战性。为了解决这个问题,我们采用了双样本孟德尔随机化方法.
■我们从全基因组关联研究中选择了这些风险因素的遗传工具,这些研究包括3,383,199个个体在全基因组显著性水平(p<5×10-9)。动脉硬度数据来自英国生物库,其中包括127,121名参与者。我们的主要分析使用逆方差加权方法来探索因果关系。为了证实我们的结果的稳健性,我们使用Egger回归进行了敏感性分析,加权中位数法,和孟德尔随机化多效度测量和异常值(MR-PRESSO)。
■我们的分析显示,开始吸烟的遗传倾向与动脉僵硬指数的增加之间存在显着关联(β=0.11;95%置信区间[CI],0.06至0.16;p=1.95×10-5)。此外,基因预测的每日香烟数量与动脉僵硬指数之间存在暗示性联系(β=0.05;95%CI,5.25×10-4~0.10;p=4.75×10-2).在遗传预测的开始吸烟年龄之间没有观察到因果关系,戒烟,或饮酒和动脉僵硬指数的风险。
■这项孟德尔随机化研究表明,开始吸烟可能是动脉僵硬的致病危险因素。然而,需要进一步的研究来确定日常香烟的数量是否直接有助于动脉僵硬的发展。关于酒精消费,开始吸烟的年龄,戒烟,没有足够的证据证明因果关系。
UNASSIGNED: While observational studies have demonstrated connections between cigarette smoking, alcohol consumption, and arterial stiffness, establishing a causal relationship has proven challenging because of potential confounding factors. To address this problem, we employed a two-sample Mendelian randomization approach.
UNASSIGNED: We selected genetic instruments for these risk factors from genome-wide association studies encompassing 3,383,199 individuals at the genome-wide significance level (p < 5 × 10 - 9 ). Arterial stiffness data were acquired from the UK Biobank, which included 127,121 participants. Our primary analysis utilized the inverse variance-weighted method to explore causality. To confirm our results\' robustness, we conducted sensitivity analyses using Egger regression, the weighted median method, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO).
UNASSIGNED: Our analysis revealed a significant association between genetic inclination to smoking initiation and an increase in the arterial stiffness index ( β = 0.11; 95% confidence interval [CI], 0.06 to 0.16; p = 1.95 × 10 - 5 ). Additionally, there was a suggestive connection between genetically predicted number of cigarettes per day and the arterial stiffness index ( β = 0.05; 95% CI, 5.25 × 10 - 4 to 0.10; p = 4.75 × 10 - 2 ). No causal relationships were observed between the genetically predicted age of smoking initiation, smoking cessation, or alcohol consumption and the risk of arterial stiffness index.
UNASSIGNED: This Mendelian randomization study indicates that smoking initiation is likely a causative risk factor for arterial stiffness. However, further research is needed to determine if the quantity of daily cigarettes directly contributes to arterial stiffness development. Regarding alcohol consumption, age of smoking initiation, and smoking cessation, there was insufficient evidence to establish causality.