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However, the casual relationship between smoking, passive smoking, alcohol consumption, and atrial fibrillation (AF) remains uncertain. Conventional observational studies are difficult to draw conclusion on high-quality causality. To elucidate the association between smoking, secondhand smoke exposure, alcohol consumption, and AF, we conducted this two-sample Mendelian randomization (MR) analysis. Smoking encompasses current tobacco smoking, ever-smoked, and light smokers, with light smokers being defined as at least 100 smokes in lifetime, as well as secondhand smoke exposure, which is characterized by workplace had a lot of cigarette smoke from other people smoking: Often. Alcohol consumption encompasses diagnoses\u2014secondary ICD10: Z72.1 Alcohol use and the frequency of alcohol intake. Genetic variants associated with smoking and alcohol consumption were obtained from the IEU Open GWAS project and subsequently selected as instrumental variables (IVs). The corresponding variants associated with AF were also retrieved from the IEU Open GWAS project. The primary MR method utilized was the inverse-variance weighted (IVW). To assess the robustness of our results, multiple supplementary methods were utilized, including the weighted median (WM), MR-Egger regression, MR-PRESSO, MR-Egger intercept test, and the leave-one-out method. A reverse MR analysis was also conducted to determine the potential existence of reverse causality. Genetic predictions indicate a causal relationship between active smoking (current tobacco smoking, <jats:italic>P<\/jats:italic>\n            <jats:sub>\n              <jats:italic>-val<\/jats:italic>\n            <\/jats:sub>\u2009=\u20090.019, OR: 1.413, 95% CI\u2009=\u20091.058\u20131.888; ever smoked, <jats:italic>P<\/jats:italic>\n            <jats:sub>\n              <jats:italic>-val<\/jats:italic>\n            <\/jats:sub>\u2009=\u20090.049, OR: 1.355, 95% CI\u2009=\u20091.001\u20131.834; light smokers, <jats:italic>P<\/jats:italic>\n            <jats:sub>\n              <jats:italic>-val<\/jats:italic>\n            <\/jats:sub>\u2009=\u20090.001, OR: 1.444, 95% CI\u2009=\u20091.154\u20131.806) and AF. No causal association was found between secondhand smoke exposure, alcohol consumption phenotypes, and AF. Additionally, the reverse MR analysis did not reveal any evidence of reverse causality from AF to active smoking. This study provides MR evidence supporting a causal association between active smoking and AF. The significance of smoking cessation is underscored by its potential to prevent or mitigate the risk of AF. Furthermore, the impact of secondhand smoke exposure and alcohol consumption on AF, as well as the causality among these factors, warrants further investigation.<\/jats:p>","DOI":"10.1007\/s12012-025-09964-8","type":"journal-article","created":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T21:04:18Z","timestamp":1740258258000},"page":"341-353","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Smoking, Alcohol Consumption, and Atrial Fibrillation: Mendelian Randomization Study"],"prefix":"10.1007","volume":"25","author":[{"given":"Xuejiao","family":"Ye","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianyu","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinzheng","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingtian","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,22]]},"reference":[{"issue":"13","key":"9964_CR1","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1177\/2047487318780435","volume":"25","author":"D Aune","year":"2018","unstructured":"Aune, D., Schlesinger, S., Norat, T., & Riboli, E. 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