Mendelian randomization analyses of smoking and Alzheimer's disease in Chinese and Japanese populations

Yuan Zhu; Ying Guan; Xuewen Xiao; Bin Jiao; Xinxin Liao; Hui Zhou; Xixi Liu; Feiyan Qi; Qiyuan Peng; Lu Zhou; Tianyan Xu; Qijie Yang; Sizhe Zhang; Meng Li; Zhouhai Zhu; Sheming Lu; Jinchen Li; Beisha Tang; Lu Shen; Jianhua Yao; Yafang Zhou

doi:10.3389/fnagi.2023.1157051

Mendelian randomization analyses of smoking and Alzheimer's disease in Chinese and Japanese populations

Front Aging Neurosci. 2023 May 12:15:1157051. doi: 10.3389/fnagi.2023.1157051. eCollection 2023.

Authors

Yuan Zhu¹, Ying Guan², Xuewen Xiao¹, Bin Jiao^{1

3

4}, Xinxin Liao^{3

4

5}, Hui Zhou¹, Xixi Liu¹, Feiyan Qi², Qiyuan Peng², Lu Zhou¹, Tianyan Xu¹, Qijie Yang¹, Sizhe Zhang¹, Meng Li², Zhouhai Zhu², Sheming Lu², Jinchen Li⁶, Beisha Tang^{1

4}, Lu Shen^{1

3

4}, Jianhua Yao², Yafang Zhou^{3

4

5}

Affiliations

¹ Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
² Joint Institute of Tobacco and Health, Kunming, Yunnan, China.
³ Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, China.
⁴ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
⁵ Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, China.
⁶ Bioinformatics Center & National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.

Abstract

Background: Previous epidemiological studies have reported controversial results on the relationship between smoking and Alzheimer's disease (AD). Therefore, we sought to assess the association using Mendelian randomization (MR) analysis.

Methods: We used single nucleotide polymorphisms (SNPs) associated with smoking quantity (cigarettes per day, CPD) from genome-wide association studies (GWAS) of Japanese population as instrumental variables, then we performed two-sample MR analysis to investigate the association between smoking and AD in a Chinese cohort (1,000 AD cases and 500 controls) and a Japanese cohort (3,962 AD cases and 4,074 controls), respectively.

Results: Genetically higher smoking quantity showed no statistical causal association with AD risk (the inverse variance weighted (IVW) estimate in the Chinese cohort: odds ratio (OR) = 0.510, 95% confidence interval (CI) = 0.149-1.744, p = 0.284; IVW estimate in the Japanese cohort: OR = 1.170, 95% confidence interval CI = 0.790-1.734, p = 0.434).

Conclusion: This MR study, for the first time in Chinese and Japanese populations, found no significant association between smoking and AD.

Keywords: Alzheimer’s disease; East Asian population; causal association; smoking; two-sample Mendelian randomization analysis.