BACKGROUND The causal role of alcohol consumption for cardiovascular disease remains unclear. We used Mendelian randomization (MR) to predict the effect of alcohol consumption on 8 cardiovascular diseases. METHODS Up to 94 single-nucleotide polymorphisms were used as instrumental variables for alcohol consumption. Genetic association estimates for cardiovascular diseases were obtained from large-scale consortia and UK Biobank. Analyses were conducted using the inverse variance-weighted, weighted median, MR-PRESSO, MR-Egger, and multivariable MR methods. RESULTS Genetically predicted alcohol consumption was consistently associated with stroke and peripheral artery disease across the different analyses. The odds ratios (ORs) per 1-SD increase of log-transformed alcoholic drinks per week were 1.27 ([95% CI, 1.12-1.45] P=2.87×10-4) for stroke and 3.05 ([95% CI, 1.92-4.85] P=2.30×10-6) for peripheral artery disease in the inverse variance-weighted analysis. There was some evidence for positive associations of genetically predicted alcohol consumption with coronary artery disease (OR, 1.16 [95% CI, 1.00-1.36]; P=0.052), atrial fibrillation (OR, 1.17 [95% CI, 1.00-1.37]; P=0.050), and abdominal aortic aneurysm (OR, 2.60 [95% CI, 1.15-5.89]; P=0.022) in the inverse variance-weighted analysis. These associations were somewhat attenuated in multivariable MR analysis adjusted for smoking initiation. There was no evidence of associations of genetically predicted alcohol consumption with heart failure (OR, 1.00 [95% CI, 0.68-1.47]; P=0.996), venous thromboembolism (OR, 1.04 [95% CI, 0.77-1.39]; P=0.810), and aortic valve stenosis (OR, 1.03 [95% CI, 0.56-1.90]; P=0.926). CONCLUSIONS This study provides evidence of a causal relationship between higher alcohol consumption and increased risk of stroke and peripheral artery disease. The causal role of alcohol consumption for other cardiovascular diseases requires further research.

中文翻译：

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饮酒与心血管疾病：孟德尔随机研究。

背景 饮酒对心血管疾病的因果作用仍不清楚。我们使用孟德尔随机化 (MR) 来预测饮酒对 8 种心血管疾病的影响。方法 多达 94 个单核苷酸多态性被用作酒精消耗的工具变量。心血管疾病的遗传关联估计来自大型财团和英国生物银行。使用逆方差加权、加权中位数、MR-PRESSO、MR-Egger 和多变量 MR 方法进行分析。结果 在不同的分析中，基因预测的饮酒量始终与中风和外周动脉疾病相关。每周对数转换的酒精饮料每增加 1-SD 的优势比 (OR) 分别为 1.27 ([95% CI, 1.12-1.45] P=2.87×10-4) 和 3. 05 ([95% CI, 1.92-4.85] P=2.30×10-6) 外周动脉疾病在逆方差加权分析中。有一些证据表明，基因预测的饮酒与冠状动脉疾病（OR，1.16 [95% CI，1.00-1.36]；P=0.052）、心房颤动（OR，1.17 [95% CI，1.00-1.37]）呈正相关; P=0.050) 和腹主动脉瘤 (OR, 2.60 [95% CI, 1.15-5.89]; P=0.022) 在逆方差加权分析中。在针对吸烟开始调整的多变量 MR 分析中，这些关联有所减弱。没有证据表明基因预测的饮酒与心力衰竭（OR，1.00 [95% CI，0.68-1.47]；P=0.996）、静脉血栓栓塞（OR，1.04 [95% CI，0.77-1.39]；P =0.810）和主动脉瓣狭窄（OR，1.03 [95% CI，0.56-1.90]；P=0.926）。结论 本研究提供了证据表明较高的饮酒量与中风和外周动脉疾病风险增加之间存在因果关系。饮酒对其他心血管疾病的因果作用需要进一步研究。