{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T14:40:16Z","timestamp":1762353616776,"version":"3.41.2"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"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. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Epidemiological evidence suggests that non-alcoholic fatty liver disease (NAFLD) may increase the risk of atrial fibrillation (AF). However, the findings are inconsistent, and the causality remains to be established.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted two-step, two-sample Mendelian randomization (MR) analysis to assess the association between genetically predicted NAFLD (i.e. chronically elevated serum alanine aminotransferase levels [cALT], imaging-based and biopsy-confirmed NAFLD) and AF. Subsequently, we further performed Mendelian randomization to investigate the causal relationship between non-alcoholic steatohepatitis (NASH), a subtype of NAFLD, and AF. The inverse variance weighted (IVW) method was used as the primary approach to reveal the potential causation between the exposure and outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>There was no significant causal association between NAFLD diagnosed based on cALT, confirmed by imaging, or verified by biopsy, and an increased risk of atrial fibrillation. Furthermore, the results of the IVW method revealed a positive causal effect of NASH on AF (OR=1.113, 95% CI=1.025-1.209, P = 0.011). In the reverse analysis, however, no evidence supported a significant genetic association between AF and NASH (OR=0.974, 95% CI=0.934-1.016, P = 0.214).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A causal relationship existed between NASH and the risk of AF. However, no significant genetic association has been observed between NAFLD and AF risk. This suggests that managing the progression of NAFLD may hold potential value in preventing the onset of AF.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1390259","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T05:21:13Z","timestamp":1742275273000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A Mendelian randomization study reveals a causal association between NASH and the risk of atrial fibrillation"],"prefix":"10.3389","volume":"16","author":[{"given":"Biwei","family":"Cheng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuekang","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jue","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanghui","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingtai","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumeng","family":"Yi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojuan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.11.004","article-title":"Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease","volume":"64","year":"2016","journal-title":"J Hepatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29367","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.12.012","article-title":"NAFLD: a multisystem disease","volume":"62","author":"Byrne","year":"2015","journal-title":"J Hepatol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1053\/j.gastro.2019.11.312","article-title":"MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease","volume":"158","author":"Eslam","year":"2020","journal-title":"Gastroenterology"},{"key":"B5","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1161\/CIRCRESAHA.120.316340","article-title":"Epidemiology of atrial fibrillation in the 21st century: novel methods and new insights","volume":"127","author":"Kornej","year":"2020","journal-title":"Circ Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14044","article-title":"Association between non-alcoholic fatty liver disease and risk of atrial fibrillation in adult individuals: An updated meta-analysis","volume":"39","author":"Mantovani","year":"2019","journal-title":"Liver Int"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14236","article-title":"Association between non-alcoholic fatty liver disease and risk of new-onset atrial fibrillation in healthy adults","volume":"40","author":"Roh","year":"2020","journal-title":"Liver Int"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14461","article-title":"Nonalcoholic fatty liver disease is associated with increased risk of atrial fibrillation","volume":"40","author":"Cai","year":"2020","journal-title":"Liver Int"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.1142","article-title":"Link between non-alcoholic fatty liver disease and atrial fibrillation: A systematic review and meta-analysis","volume":"9","author":"Minhas","year":"2017","journal-title":"Cureus"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-019-01780-2","article-title":"Circadian rhythms: a possible new player in non-alcoholic fatty liver disease pathophysiology","volume":"97","author":"Gnocchi","year":"2019","journal-title":"J Mol Med (Berl)"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/cells12121582","article-title":"Circadian disruption primes myofibroblasts for accelerated activation as a mechanism underpinning fibrotic progression in non-alcoholic fatty liver disease","volume":"12","author":"Jokl","year":"2023","journal-title":"Cells"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00300.2015","article-title":"Circadian variation of variability and irregularity of heart rate in patients with permanent atrial fibrillation: relation to symptoms and rate control drugs","volume":"309","author":"Corino","year":"2015","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2019.09.002","article-title":"Atrial fibrillation and heart failure with preserved ejection fraction in patients with nonalcoholic fatty liver disease","volume":"133","author":"Packer","year":"2020","journal-title":"Am J Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s43586-021-00092-5","article-title":"Mendelian randomization","volume":"2","author":"Sanderson","year":"2022","journal-title":"Nat Rev Methods Primers"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01078-z","article-title":"A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation","volume":"54","author":"Vujkovic","year":"2022","journal-title":"Nat Genet"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05473-8","article-title":"FinnGen provides genetic insights from a well-phenotyped isolated population","volume":"613","author":"Kurki","year":"2023","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0171-3","article-title":"Biobank-driven genomic discovery yields new insight into atrial fibrillation biology","volume":"50","author":"Nielsen","year":"2018","journal-title":"Nat Genet"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0142937","article-title":"Non-alcoholic fatty liver disease as a predictor of atrial fibrillation in middle-aged population (OPERA study)","volume":"10","author":"Karajamaki","year":"2015","journal-title":"PloS One"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1160532","article-title":"A systematic review and meta-analysis of cohort studies on the potential association between NAFLD\/MAFLD and risk of incident atrial fibrillation","volume":"14","author":"Zhou","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.832023","article-title":"Non-alcoholic fatty liver disease and the risk of incident atrial fibrillation in young adults: A nationwide population-based cohort study","volume":"9","author":"Choi","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.5114\/aic.2017.70198","article-title":"Nonalcoholic fatty liver disease as a predictor of atrial fibrillation: a systematic review and meta-analysis","volume":"13","author":"Zhou","year":"2017","journal-title":"Postepy Kardiol Interwencyjnej"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinre.2017.08.001","article-title":"The association between non-alcoholic fatty liver disease and atrial fibrillation: A meta-analysis","volume":"41","author":"Wijarnpreecha","year":"2017","journal-title":"Clin Res Hepatol Gastroenterol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14018","article-title":"Atrial fibrillation is highly prevalent yet undertreated in patients with biopsy-proven nonalcoholic steatohepatitis","volume":"39","author":"Whitsett","year":"2019","journal-title":"Liver Int"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.005227","article-title":"Relations of liver fat with prevalent and incident atrial fibrillation in the framingham heart study","volume":"6","author":"Long","year":"2017","journal-title":"J Am Heart Assoc"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.10.032","article-title":"Assessing causal relationship between non-alcoholic fatty liver disease and risk of atrial fibrillation","volume":"78","author":"Li","year":"2023","journal-title":"J Hepatol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2022.07.007","article-title":"Causal effect of non-alcoholic fatty liver disease on atrial fibrillation","volume":"105","author":"Chen","year":"2022","journal-title":"Eur J Intern Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0010-0","article-title":"Risk of cardiomyopathy and cardiac arrhythmias in patients with nonalcoholic fatty liver disease","volume":"15","author":"Anstee","year":"2018","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-320622","article-title":"NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications","volume":"69","author":"Targher","year":"2020","journal-title":"Gut"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.20524\/aog.2020.0550","article-title":"Nonalcoholic fatty liver disease and atrial fibrillation: possible pathophysiological links and therapeutic interventions","volume":"33","author":"Haghbin","year":"2020","journal-title":"Ann Gastroenterol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.ijcard.2013.08.078","article-title":"Association of inflammatory factors with occurrence and recurrence of atrial fibrillation: a meta-analysis","volume":"169","author":"Wu","year":"2013","journal-title":"Int J Cardiol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.02.066","article-title":"Pathogenesis of nonalcoholic steatohepatitis","volume":"150","author":"MaChado","year":"2016","journal-title":"Gastroenterology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"5023","DOI":"10.1038\/s41598-020-61750-4","article-title":"The risk of atrial fibrillation in patients with non-alcoholic fatty liver disease and a high hepatic fibrosis index","volume":"10","author":"Park","year":"2020","journal-title":"Sci Rep"},{"key":"B33","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1002\/hep.20280","article-title":"Beyond insulin resistance in NASH: TNF-alpha or adiponectin","volume":"40","author":"Hui","year":"2004","journal-title":"Hepatology"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1390259\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T05:21:16Z","timestamp":1742275276000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1390259\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,18]]},"references-count":33,"alternative-id":["10.3389\/fendo.2025.1390259"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1390259","relation":{},"ISSN":["1664-2392"],"issn-type":[{"type":"electronic","value":"1664-2392"}],"subject":[],"published":{"date-parts":[[2025,3,18]]},"article-number":"1390259"}}