RT Journal Article SR Electronic T1 Tobacco and alcohol consumption and the risk of frailty and falling: a Mendelian randomisation study JF Journal of Epidemiology and Community Health JO J Epidemiol Community Health FD BMJ Publishing Group Ltd SP 349 OP 354 DO 10.1136/jech-2022-219855 VO 77 IS 6 A1 Guo, Xingzhi A1 Tang, Peng A1 Zhang, Lina A1 Li, Rui YR 2023 UL http://jech.bmj.com/content/77/6/349.abstract AB Background Epidemiological data have suggested that tobacco and alcohol consumption were associated with the risk of frailty and falling, but it is yet unclear whether these associations are of a causal nature. Thus, we conducted two-sample Mendelian randomisation analysis using genetic instruments to determine the causal associations of tobacco and alcohol consumption on frailty and falls.Methods Independent instrumental variables strongly (p<5E–09) associated with tobacco and alcohol consumption were obtained from the genome-wide association study (GWAS) and Sequencing Consortium of Alcohol and Nicotine use (up to 2 669 029 participants). Summary statistics of the frailty index (FI, N=175 226) and falling risk (N=451 179) were from the two latest published GWAS datasets on FI and falling risk.Results Using the inverse-variance weighted method, our results showed that genetically determined initiation of smoking was significantly associated with an increased FI (β=0.34, 95% CI=0.29 to 0.40, p=5.48E–33) and risk of falling (OR=1.39, 95% CI=1.30 to 1.50, p=1.01E–20). In addition, the age of initiation of smoking and cigarettes consumption per day was negatively and positively associated with both FI and falls, respectively. Current smokers were prone to having a higher FI and falling risk than individuals who quit smoking. There was no significant causal association between alcohol use and the risk of frailty and falling. Similar results were obtained using other statistical approaches with good stability.Conclusions Our findings demonstrate that tobacco use, but not alcohol drinking, significantly increases the risk of frailty and falling. Future studies are warranted to clarify the underlying physiopathological mechanisms.All data relevant to the study are included in the article or uploaded as online supplemental information. Not applicable.