Determination of genetic correlation between tobacco smoking and coronary artery disease

Zhouhai Zhu; Qiang Liu; Meng Li; Yinghao Yao; Feiyan Qi; Yi Xu; Sheming Lu; Zhongli Yang; Ying Guan; Ming D Li; Jianhua Yao

doi:10.3389/fpsyt.2023.1279962

Determination of genetic correlation between tobacco smoking and coronary artery disease

Front Psychiatry. 2023 Sep 26:14:1279962. doi: 10.3389/fpsyt.2023.1279962. eCollection 2023.

Authors

Zhouhai Zhu¹, Qiang Liu², Meng Li¹, Yinghao Yao², Feiyan Qi¹, Yi Xu², Sheming Lu¹, Zhongli Yang², Ying Guan¹, Ming D Li², Jianhua Yao¹

Affiliations

¹ Joint Institute of Tobacco and Health, Kunming, Yunnan, China.
² State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

Abstract

Backgrounds: Tobacco smoking is an important risk factor for coronary artery disease (CAD), but the genetic mechanisms linking smoking to CAD remain largely unknown.

Methods: We analyzed summary data from the genome-wide association study (GWAS) of the UK Biobank for CAD, plasma lipid concentrations (n = 184,305), and smoking (n = 337,030) using different biostatistical methods, which included LD score regression and Mendelian randomization (MR).

Results: We identified SNPs shared by CAD and at least one smoking behavior, the genes where these SNPs are located were found to be significantly enriched in the processes related to lipoprotein metabolic, chylomicron-mediated lipid transport, lipid digestion, mobilization, and transport. The MR analysis revealed a positive correlation between smoking cessation and decreased risk for CAD when smoking cessation was considered as exposure (p = 0.001), and a negative correlation between the increased risk for CAD and smoking cessation when CAD was considered as exposure (p = 2.95E-08). This analysis further indicated that genetic liability for smoking cessation increased the risk of CAD.

Conclusion: These findings inform the concomitant conditions of CAD and smoking and support the idea that genetic liabilities for smoking behaviors are strongly associated with the risk of CAD.

Keywords: CAD; coronary artery disease; genome-wide association study; mendelian randomization analysis; smoking.