Xue Angli, Zhu Zhihong, Wang Huanwei, Jiang Longda, Visscher Peter M, Zeng Jian, Yang Jian
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia.
Commun Med (Lond). 2024 Mar 12;4(1):43. doi: 10.1038/s43856-024-00473-3.
Substance use behaviours (SUB) including smoking, alcohol consumption, and coffee intake are associated with many health outcomes. However, whether the health effects of SUB are causal remains controversial, especially for alcohol consumption and coffee intake.
In this study, we assess 11 commonly used Mendelian Randomization (MR) methods by simulation and apply them to investigate the causal relationship between 7 SUB traits and health outcomes. We also combine stratified regression, genetic correlation, and MR analyses to investigate the dosage-dependent effects.
We show that smoking initiation has widespread risk effects on common diseases such as asthma, type 2 diabetes, and peripheral vascular disease. Alcohol consumption shows risk effects specifically on cardiovascular diseases, dyslipidemia, and hypertensive diseases. We find evidence of dosage-dependent effects of coffee and tea intake on common diseases (e.g., cardiovascular disease and osteoarthritis). We observe that the minor allele effect of rs4410790 (the top signal for tea intake level) is negative on heavy tea intake but positive on moderate tea intake , compared to the non-tea-drinkers.
Our study reveals the complexity of the health effects of SUB and informs design for future studies aiming to dissect the causal relationships between behavioural traits and complex diseases.
包括吸烟、饮酒和咖啡摄入在内的物质使用行为（SUB）与许多健康结果相关。然而，SUB对健康的影响是否具有因果关系仍存在争议，尤其是饮酒和咖啡摄入方面。
在本研究中，我们通过模拟评估了11种常用的孟德尔随机化（MR）方法，并将其应用于研究7种SUB特征与健康结果之间的因果关系。我们还结合分层回归、遗传相关性和MR分析来研究剂量依赖性效应。
我们表明，开始吸烟对哮喘、2型糖尿病和外周血管疾病等常见疾病具有广泛的风险影响。饮酒对心血管疾病、血脂异常和高血压疾病具有特定的风险影响。我们发现咖啡和茶的摄入量对常见疾病（如心血管疾病和骨关节炎）存在剂量依赖性效应的证据。我们观察到，与不喝茶的人相比，rs4410790（茶摄入量水平的最强信号）的次要等位基因效应在大量饮茶时为负，但在适量饮茶时为正。
我们的研究揭示了SUB对健康影响的复杂性，并为未来旨在剖析行为特征与复杂疾病之间因果关系的研究设计提供了信息。
