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

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.