{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:32:33Z","timestamp":1791066753796,"version":"4.1.0"},"reference-count":39,"publisher":"BMJ","issue":"6","funder":[{"name":"Project for Sanqin Academic Innovation Team in Shaanxi Province","award":["SQ0157"],"award-info":[{"award-number":["SQ0157"]}]},{"name":"Fundamental Research Funds for the Central Universities, Xi'an Jiaotong University","award":["XZY012022136"],"award-info":[{"award-number":["XZY012022136"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Epidemiol Community Health"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Independent instrumental variables strongly (p&lt;5E\u201309) 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\u2009669\u2009029 participants). Summary statistics of the frailty index (FI, N=175\u2009226) and falling risk (N=451\u2009179) were from the two latest published GWAS datasets on FI and falling risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using the inverse-variance weighted method, our results showed that genetically determined initiation of smoking was significantly associated with an increased FI (\u03b2=0.34, 95% CI=0.29 to 0.40, p=5.48E\u201333) and risk of falling (OR=1.39, 95% CI=1.30 to 1.50, p=1.01E\u201320). 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 stabilit<jats:underline>y<\/jats:underline>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jech-2022-219855","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T17:24:05Z","timestamp":1680283445000},"page":"349-354","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":37,"title":["Tobacco and alcohol consumption and the risk of frailty and falling: a Mendelian randomisation study"],"prefix":"10.1136","volume":"77","author":[{"given":"Xingzhi","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2318-9232","authenticated-orcid":false,"given":"Rui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2023,3,31]]},"reference":[{"key":"2023051002101361000_77.6.349.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)31786-6"},{"key":"2023051002101361000_77.6.349.2","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1093\/ageing\/afaa112","article-title":"Frailty, a multisystem ageing syndrome","volume":"49","author":"Thillainadesan","year":"2020","journal-title":"Age Ageing"},{"key":"2023051002101361000_77.6.349.3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1080\/17425255.2021.1839413","article-title":"Alterations in drug disposition in older adults: a focus on geriatric syndromes","volume":"17","author":"Maher","year":"2021","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"2023051002101361000_77.6.349.4","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1111\/jnu.12322","article-title":"Frailty as a risk factor for falls among community dwelling people: evidence from a meta-analysis","volume":"49","author":"Cheng","year":"2017","journal-title":"J Nurs Scholarsh"},{"key":"2023051002101361000_77.6.349.5","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1530\/EC-20-0405","article-title":"Association between frailty and risk of fall among diabetic patients","volume":"9","author":"Wang","year":"2020","journal-title":"Endocr Connect"},{"key":"2023051002101361000_77.6.349.6","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1093\/ageing\/afaa219","article-title":"Prevalence of frailty in 62 countries across the world: a systematic review and meta-analysis of population-level studies","volume":"50","author":"O\u2019Caoimh","year":"2021","journal-title":"Age Ageing"},{"key":"2023051002101361000_77.6.349.7","doi-asserted-by":"crossref","first-page":"224","DOI":"10.37268\/mjphm\/vol.20\/no.2\/art.304","article-title":"THE economic burden of frailty among elderly people: a review of THE current literature","volume":"20","author":"Ismail","year":"2020","journal-title":"MJPHM"},{"key":"2023051002101361000_77.6.349.8","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1186\/s12877-015-0134-9","article-title":"Smoking as a predictor of frailty: a systematic review","volume":"15","author":"Kojima","year":"2015","journal-title":"BMC Geriatr"},{"key":"2023051002101361000_77.6.349.9","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1093\/ageing\/afx165","article-title":"Alcohol consumption in midlife and old age and risk of frailty: alcohol paradox in a 30-year follow-up study","volume":"47","author":"Strandberg","year":"2018","journal-title":"Age Ageing"},{"key":"2023051002101361000_77.6.349.10","doi-asserted-by":"crossref","first-page":"102815","DOI":"10.1520\/JAI102815","article-title":"Gender-Specific effects of smoking and alcohol consumption on the risk of falling in downhill skiers","volume":"7","author":"Burtscher","year":"2010","journal-title":"J ASTM Int"},{"key":"2023051002101361000_77.6.349.11","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1093\/ageing\/afx136","article-title":"Does current smoking predict future frailty? the English longitudinal study of ageing","volume":"47","author":"Kojima","year":"2018","journal-title":"Age Ageing"},{"key":"2023051002101361000_77.6.349.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2013.12.002"},{"key":"2023051002101361000_77.6.349.13","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00198-014-2904-1","article-title":"Dysmobility syndrome and mortality risk in US men and women age 50 years and older","volume":"26","author":"Looker","year":"2015","journal-title":"Osteoporos Int"},{"key":"2023051002101361000_77.6.349.14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s43586-021-00092-5","article-title":"Mendelian randomization","volume":"2","author":"Sanderson","year":"2022","journal-title":"Nat Rev Methods Primers"},{"key":"2023051002101361000_77.6.349.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05477-4"},{"key":"2023051002101361000_77.6.349.16","doi-asserted-by":"crossref","unstructured":"Atkins JL , Jylh\u00e4v\u00e4 J , Pedersen NL , et al . A genome-wide association study of the frailty index highlights brain pathways in ageing. Aging Cell 2021;20:e13459. doi:10.1111\/acel.13459","DOI":"10.1111\/acel.13459"},{"key":"2023051002101361000_77.6.349.17","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2318-8-1"},{"key":"2023051002101361000_77.6.349.18","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/s42003-020-01256-x","article-title":"Genetic basis of falling risk susceptibility in the UK biobank study","volume":"3","author":"Trajanoska","year":"2020","journal-title":"Commun Biol"},{"key":"2023051002101361000_77.6.349.19","doi-asserted-by":"crossref","unstructured":"Ye T , Shao J , Kang H . Debiased inverse-variance weighted estimator in two-sample summary-data mendelian randomization, the annals of statistics. 2021;49:2079\u2013100.","DOI":"10.1214\/20-AOS2027"},{"key":"2023051002101361000_77.6.349.20","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7"},{"key":"2023051002101361000_77.6.349.21"},{"key":"2023051002101361000_77.6.349.22","doi-asserted-by":"crossref","first-page":"110694","DOI":"10.1016\/j.pnpbp.2022.110694","article-title":"Mendelian randomization investigation highlights different roles of selenium status in mental disorders","volume":"122","author":"Guo","year":"2023","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"2023051002101361000_77.6.349.23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1053\/j.ajkd.2021.04.018","article-title":"Coffee and caffeine consumption and risk of kidney stones: a mendelian randomization study","volume":"79","author":"Yuan","year":"2022","journal-title":"Am J Kidney Dis"},{"key":"2023051002101361000_77.6.349.24","doi-asserted-by":"crossref","unstructured":"Hu X , Zhao J , Lin Z , et al . Mendelian randomization for causal inference accounting for pleiotropy and sample structure using genome-wide summary statistics. Proc Natl Acad Sci U S A 2022;119:e2106858119. doi:10.1073\/pnas.2106858119","DOI":"10.1073\/pnas.2106858119"},{"key":"2023051002101361000_77.6.349.25","doi-asserted-by":"crossref","unstructured":"Hemani G , Zheng J , Elsworth B , et al . The MR-base platform supports systematic causal inference across the human phenome. Elife 2018;7:e34408. doi:10.7554\/eLife.34408","DOI":"10.7554\/eLife.34408"},{"key":"2023051002101361000_77.6.349.26","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1007\/s40211-019-0315-4","article-title":"Systematic review and meta-analysis of the association between smoking and the incidence of frailty","volume":"33","author":"Amiri","year":"2019","journal-title":"Neuropsychiatr"},{"key":"2023051002101361000_77.6.349.27","doi-asserted-by":"crossref","unstructured":"Lando HA , Thai DT , Murray DM , et al . Age of initiation, smoking patterns, and risk in a population of working adults, preventive medicine. 1999;29:590\u20138.","DOI":"10.1006\/pmed.1999.0590"},{"key":"2023051002101361000_77.6.349.28","doi-asserted-by":"crossref","unstructured":"Hansen K , Lindstr\u00f6m M , Rosvall M . Age at smoking initiation and self-rated health among second grade high school boys and girls in scania, sweden, a cross-sectional study. BMC Public Health 2015;15:1143. doi:10.1186\/s12889-015-2457-z","DOI":"10.1186\/s12889-015-2457-z"},{"key":"2023051002101361000_77.6.349.29","first-page":"185","article-title":"Smoking in the elderly--it\u2019s never too late to quit","volume":"95","author":"Bratzler","year":"2002","journal-title":"J Okla State Med Assoc"},{"key":"2023051002101361000_77.6.349.30","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1007\/s00198-020-05508-8","article-title":"Identification of risk factors for falls in postmenopausal women: a systematic review and meta-analysis","volume":"31","author":"Zhao","year":"2020","journal-title":"Osteoporos Int"},{"key":"2023051002101361000_77.6.349.31","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1177\/2047487320902325","article-title":"Smoking status and mortality outcomes following percutaneous coronary intervention","volume":"28","author":"Parasuraman","year":"2021","journal-title":"Eur J Prev Cardiol"},{"key":"2023051002101361000_77.6.349.32","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1080\/15592294.2016.1271855","article-title":"Tobacco smoking and smoking-related DNA methylation are associated with the development of frailty among older adults","volume":"12","author":"Gao","year":"2017","journal-title":"Epigenetics"},{"key":"2023051002101361000_77.6.349.33","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.jacc.2021.11.029","article-title":"Interventions for frailty among older adults with cardiovascular disease: JACC state-of-the-art review","volume":"79","author":"Ijaz","year":"2022","journal-title":"J Am Coll Cardiol"},{"key":"2023051002101361000_77.6.349.34","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/07317115.2017.1364681","article-title":"Alcohol use and frailty risk among older adults over 12 years: the health and retirement study","volume":"41","author":"Shah","year":"2018","journal-title":"Clin Gerontol"},{"key":"2023051002101361000_77.6.349.35","first-page":"9","article-title":"Alcohol use and frailty in community-dwelling older persons aged 65 to 70 years","volume":"3","author":"Seematter-Bagnoud","year":"2014","journal-title":"J Frailty Aging"},{"key":"2023051002101361000_77.6.349.36","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12877-020-01969-y","article-title":"The association between medication or alcohol use and the incidence of frailty: a retrospective cohort study","volume":"21","author":"Jazbar","year":"2021","journal-title":"BMC Geriatr"},{"key":"2023051002101361000_77.6.349.37","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glv125"},{"key":"2023051002101361000_77.6.349.38","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.jamda.2018.10.011","article-title":"Alcohol consumption and risk of incident frailty: the english longitudinal study of aging","volume":"20","author":"Kojima","year":"2019","journal-title":"J Am Med Dir Assoc"},{"key":"2023051002101361000_77.6.349.39","doi-asserted-by":"publisher","DOI":"10.1093\/ageing\/afx086"}],"container-title":["Journal of Epidemiology and Community Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jech-2022-219855","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T16:02:07Z","timestamp":1683734527000},"score":1,"resource":{"primary":{"URL":"https:\/\/jech.bmj.com\/lookup\/doi\/10.1136\/jech-2022-219855"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,31]]},"references-count":39,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,5,10]]},"published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1136\/jech-2022-219855"],"URL":"https:\/\/doi.org\/10.1136\/jech-2022-219855","relation":{},"ISSN":["0143-005X","1470-2738"],"issn-type":[{"value":"0143-005X","type":"print"},{"value":"1470-2738","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,31]]}}}