{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T12:25:29Z","timestamp":1776947129596,"version":"3.51.4"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T00:00:00Z","timestamp":1726185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"Background<\/jats:title>Aneurysmal subarachnoid hemorrhage (aSAH) represents a critical health concern characterized by elevated mortality and morbidity rates. Although both genetic predisposition and lifestyle choices influence aSAH susceptibility, understanding the causative associations between cigarette smoking, alcohol consumption, and aSAH risk remains imperative. Mendelian randomization (MR) offers a robust methodological framework for dissecting these associations, leveraging genetic variants as instrumental variables.<\/jats:p><\/jats:sec>Objective<\/jats:title>In this study, a two-sample Mendelian randomization (TSMR) approach was employed to elucidate the causal connections between genetically determined cigarette smoking, alcohol consumption, and aSAH risk.<\/jats:p><\/jats:sec>Methods<\/jats:title>Genetic instruments associated with cigarette smoking and alcohol consumption were sourced from the genome-wide association study (GWAS) and Sequencing Consortium of Alcohol and Nicotine use (GSCAN). Using a genome-wide association study (GWAS) dataset that encompassed aSAH cases and controls of European ancestry, TSMR, which utilized the inverse variance weighting (IVW) method, was employed to estimate the causal effects. Rigorous criteria were applied for selecting instrumental variables to ensure a robust Mendelian randomization analysis.<\/jats:p><\/jats:sec>Results<\/jats:title>A significant causal association was found between genetically determined cigarette smoking and an increased risk of aSAH, with a 1-standard deviation (SD) increase in cigarette use genetically linked to a 96% relative risk elevation [OR-IVW = 1.96, 95% confidence interval (CI) = 1.28\u20133.01, p<\/jats:italic> = 0.0021]. However, genetically determined alcohol consumption did not exhibit a statistically significant association with aSAH risk (OR-IVW = 1.22, 95% CI = 0.61\u20132.45, p<\/jats:italic> = 0.578).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>The Mendelian randomization analysis revealed a causal nexus between cigarette smoking and an increased risk of aSAH, advocating for targeted smoking cessation interventions within genetically predisposed cohorts. The results regarding the relationship between alcohol consumption and aSAH were affected by insufficient statistical power. A prudent interpretation of the findings highlights the limitations of Mendelian randomization in elucidating intricate genetic epidemiological relationships. Ongoing research involving larger cohort sizes and advanced methodological approaches is essential for comprehending the genetic underpinnings of aSAH.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnut.2024.1397776","type":"journal-article","created":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T13:50:03Z","timestamp":1726235403000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Exploring the causal links between cigarette smoking, alcohol consumption, and aneurysmal subarachnoid hemorrhage: a two-sample Mendelian randomization analysis"],"prefix":"10.3389","volume":"11","author":[{"given":"Heng","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanqing","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siwei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoao","family":"Long","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuangbin","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1111\/cns.13222","article-title":"Clinical and experimental aspects of aneurysmal subarachnoid hemorrhage","volume":"25","author":"Daou","year":"2019","journal-title":"CNS Neurosci Ther."},{"key":"B2","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1016\/S0140-6736(22)00938-2","article-title":"Spontaneous subarachnoid haemorrhage","volume":"400","author":"Claassen","year":"2022","journal-title":"Lancet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1958","DOI":"10.1161\/STROKEAHA.108.539544","article-title":"Risk factors for aneurysmal subarachnoid hemorrhage in a prospective population study: the HUNT study in Norway","volume":"40","author":"Sandvei","year":"2009","journal-title":"Stroke."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e1000058","DOI":"10.1371\/journal.pmed.1000058","article-title":"The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors","volume":"6","author":"Danaei","year":"2009","journal-title":"PLoS Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1161\/STROKEAHA.120.031622","article-title":"Genetically determined smoking behavior and risk of nontraumatic subarachnoid hemorrhage","volume":"52","author":"Acosta","year":"2021","journal-title":"Stroke."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1975","DOI":"10.1161\/STROKEAHA.116.012957","article-title":"Sex, smoking, and risk for subarachnoid hemorrhage","volume":"47","author":"Lindbohm","year":"2016","journal-title":"Stroke."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2773","DOI":"10.1161\/01.STR.0000190838.02954.e8","article-title":"Risk factors for subarachnoid hemorrhage: an updated systematic review of epidemiological studies","volume":"36","author":"Feigin","year":"2005","journal-title":"Stroke."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1161\/01.STR.0000077015.90334.A7","article-title":"Triggers of subarachnoid hemorrhage: role of physical exertion, smoking, and alcohol in the Australasian Cooperative Research on Subarachnoid Hemorrhage Study (ACROSS)","volume":"34","author":"Anderson","year":"2003","journal-title":"Stroke."},{"key":"B9","doi-asserted-by":"publisher","first-page":"k1767","DOI":"10.1136\/bmj.k1767","article-title":"Role of obesity in smoking behaviour: Mendelian randomisation study in UK Biobank","volume":"361","author":"Carreras-Torres","year":"2018","journal-title":"BMJ."},{"key":"B10","doi-asserted-by":"publisher","first-page":"a041302","DOI":"10.1101\/cshperspect.a041302","article-title":"Mendelian randomization","volume":"12","author":"Birney","year":"2022","journal-title":"Cold Spring Harb Perspect Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"13458","DOI":"10.3390\/ijms241713458","article-title":"Using Mendelian randomization to study the role of iron in health and disease","volume":"24","author":"Zeitoun","year":"2023","journal-title":"Int J Mol Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"12979","DOI":"10.1007\/s11356-022-23074-w","article-title":"Genetically predicted tobacco consumption and risk of intracranial aneurysm: a Mendelian randomization study","volume":"30","author":"Zeng","year":"2023","journal-title":"Environ Sci Pollut Res Int."},{"key":"B13","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1038\/s41586-022-05477-4","article-title":"Genetic diversity fuels gene discovery for tobacco and alcohol use","volume":"612","author":"Saunders","year":"2022","journal-title":"Nature."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1038\/s41588-020-00725-7","article-title":"Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors","volume":"52","author":"Bakker","year":"2020","journal-title":"Nat Genet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/MOL.0000000000000721","article-title":"Mendelian randomization as a tool for causal inference in human nutrition and metabolism","volume":"32","author":"Larsson","year":"2021","journal-title":"Curr Opin Lipidol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1002\/gepi.21758","article-title":"Mendelian randomization analysis with multiple genetic variants using summarized data","volume":"37","author":"Burgess","year":"2013","journal-title":"Genet Epidemiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat Genet."},{"key":"B18","doi-asserted-by":"publisher","first-page":"j5375","DOI":"10.1136\/bmj.j5375","article-title":"Modifiable pathways in Alzheimer's disease: Mendelian randomisation analysis","volume":"359","author":"Larsson","year":"2017","journal-title":"BMJ."},{"key":"B19","doi-asserted-by":"publisher","first-page":"e1003288","DOI":"10.1371\/journal.pmed.1003288","article-title":"Genetics of height and risk of atrial fibrillation: a Mendelian randomization study","volume":"17","author":"Levin","year":"2020","journal-title":"PLoS Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1161\/01.STR.0000115751.45473.48","article-title":"Active and passive smoking and the risk of subarachnoid hemorrhage: an international population-based case-control study","volume":"35","author":"Anderson","year":"2004","journal-title":"Stroke."},{"key":"B21","doi-asserted-by":"publisher","first-page":"405","DOI":"10.3171\/jns.1998.89.3.0405","article-title":"Cigarette smoking as a cause of aneurysmal subarachnoid hemorrhage and risk for vasospasm: a report of the Cooperative Aneurysm Study","volume":"89","author":"Weir","year":"1998","journal-title":"J Neurosurg."},{"key":"B22","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1136\/bmj.298.6676.789","article-title":"Meta-analysis of relation between cigarette smoking and stroke","volume":"298","author":"Shinton","year":"1989","journal-title":"BMJ."},{"key":"B23","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1161\/01.STR.14.6.857","article-title":"Saccular cerebral aneurysms in rats: a newly developed animal model of the disease","volume":"14","author":"Handa","year":"1983","journal-title":"Stroke."},{"key":"B24","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/0895-4356(91)90073-I","article-title":"Risk factors for carotid artery stenosis: an epidemiological study of men aged 69 years","volume":"44","author":"Jungquist","year":"1991","journal-title":"J Clin Epidemiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1212\/WNL.0000000000004419","article-title":"Association of intracranial aneurysm rupture with smoking duration, intensity, and cessation","volume":"89","author":"Can","year":"2017","journal-title":"Neurology."},{"key":"B26","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/S0140-6736(03)13860-3","article-title":"Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment","volume":"362","author":"Wiebers","year":"2003","journal-title":"Lancet."},{"key":"B27","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s12975-017-0557-z","article-title":"Alcohol consumption and aneurysmal subarachnoid hemorrhage","volume":"9","author":"Can","year":"2018","journal-title":"Transl Stroke Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1118980","DOI":"10.3389\/fneur.2023.1118980","article-title":"Alcohol flushing syndrome is significantly associated with intracranial aneurysm rupture in the Chinese Han population","volume":"14","author":"Chen","year":"2023","journal-title":"Front Neurol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1002\/sim.3034","article-title":"Mendelian randomization: using genes as instruments for making causal inferences in epidemiology","volume":"27","author":"Lawlor","year":"2008","journal-title":"Stat Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1093\/aje\/kwt084","article-title":"Efficient design for Mendelian randomization studies: subsample and 2-sample instrumental variable estimators","volume":"178","author":"Pierce","year":"2013","journal-title":"Am J Epidemiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"186","DOI":"10.12688\/wellcomeopenres.15555.3","article-title":"Guidelines for performing Mendelian randomization investigations: update for summer 2023","volume":"4","author":"Burgess","year":"2023","journal-title":"Wellcome Open Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"c6224","DOI":"10.1136\/bmj.c6224","article-title":"Association between general and central adiposity in childhood, and change in these, with cardiovascular risk factors in adolescence: prospective cohort study","volume":"341","author":"Lawlor","year":"2010","journal-title":"BMJ."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e1005765","DOI":"10.1371\/journal.pgen.1005765","volume":"12","author":"Gage","year":"2016","journal-title":"PLoS Genet."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2024.1397776\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T13:50:08Z","timestamp":1726235408000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2024.1397776\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,13]]},"references-count":33,"alternative-id":["10.3389\/fnut.2024.1397776"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2024.1397776","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,13]]},"article-number":"1397776"}}