Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA.
Genet Epidemiol. 2022 Apr;46(3-4):199-212. doi: 10.1002/gepi.22446. Epub 2022 Feb 16.
Coronary artery disease (CAD) is a preeminent cause of death, and smoking is a strong risk factor for CAD. Genetic factors contribute to the development of CAD, but the interplay between genetic predisposition and smoking history in CAD remains unclear. Using data from the UK Biobank, we constructed several genetic risk scores (GRSs) based on known CAD loci and assessed their interactions with smoking for the development of incident CAD in 307,147 participants of European ancestry who were free of CAD. We fitted Cox proportional hazard models and assessed gene-smoking interaction on both multiplicative and additive scales. Overall, we found no multiplicative interactions, but observed a synergistic additive interaction of GRS with both smoking status and pack-years of smoking, finding that the absolute CAD risk due to smoking was higher for those with high genetic risk. Trait-based sub-GRSs suggested smoking status and smoking intensity measured by pack-years might confer gene-smoking interaction effects with different intermediate risk factors for CAD. Our study results suggest that genetics could modify the effects of smoking on CAD and highlight the value of addressing gene-lifestyle interactions on both additive and multiplicative scales.
冠状动脉疾病 (CAD) 是主要的死亡原因，而吸烟是 CAD 的一个重要危险因素。遗传因素促成了 CAD 的发展，但遗传易感性和吸烟史在 CAD 中的相互作用仍不清楚。利用来自英国生物银行的数据，我们根据已知的 CAD 基因座构建了几个遗传风险评分 (GRS)，并评估了它们与吸烟史在欧洲血统的 307147 名无 CAD 参与者中发生 CAD 的风险之间的相互作用。我们拟合了 Cox 比例风险模型，并在乘法和加法尺度上评估了基因-吸烟相互作用。总的来说，我们没有发现乘法相互作用，但观察到 GRS 与吸烟状态和吸烟包年数之间存在协同的加法相互作用，发现高遗传风险的人因吸烟而导致的 CAD 绝对风险更高。基于性状的子 GRS 表明，吸烟状态和以包年数衡量的吸烟强度可能会对 CAD 的中间危险因素产生基因-吸烟相互作用效应。我们的研究结果表明，遗传因素可能会改变吸烟对 CAD 的影响，并强调在加法和乘法尺度上解决基因-生活方式相互作用的重要性。
