{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T09:25:03Z","timestamp":1777454703801,"version":"3.51.4"},"reference-count":27,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National High Level Hospital Clinical Research Funding","award":["2022-GSP-GG-30"],"award-info":[{"award-number":["2022-GSP-GG-30"]}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"publisher","award":["2018YFC1311201"],"award-info":[{"award-number":["2018YFC1311201"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People\u2019s Republic of China","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Although prior observational studies have suggested that patients with non-alcoholic fatty liver disease (NAFLD) may have a higher risk of coronary artery calcification (CAC), these findings remain controversial. This study aimed to explore the causal association between NAFLD and CAC at genetic level by two-sample Mendelian randomization (MR) analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Utilizing summary-level data from multiple large-scale genome-wide association studies in European populations, a two-sample MR analysis was initially conducted to explore the potential causal association between NAFLD and CAC. The results of the MR analysis were pooled through random-effect meta-analysis. The inverse variance weighting method served as the primary approach for MR analysis. Additionally, the weighted median, MR-Egger, and MR-pleiotropy residual sum and outlier methods were applied for sensitivity analysis. Summary-level data on liver fatty content was utilized for validation analysis, while summary-level data on cirrhosis served as positive control, further ensuring the validity and robustness of our findings. Reverse MR analysis was performed to assess the association between CAC and NAFLD, employing instrument variables derived from CAC. The MR analysis indicated that genetically predicted NAFLD had no effects on the risk of CAC [Beta: 0.01, 95% confidence interval (CI): \u22120.02 to 0.03, P = 0.74]. Likewise, the reverse MR analysis found no significant genetic association between CAC and NAFLD (odds ratio: 1.00, 95% CI: 0.96\u20131.06, P = 0.88). Validation analysis yielded consistent results, showing no significant association between fatty liver content and CAC.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our two-sample MR analysis did not support that there is a causal association between NAFLD and CAC at genetic level. The association between NAFLD and CAC reported in some previous observational studies may rely on NAFLD complicated with metabolic disorders, rather than being directly linked to the hepatic steatosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwae336","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T11:53:37Z","timestamp":1728906817000},"source":"Crossref","is-referenced-by-count":7,"title":["The association between non-alcoholic liver fatty disease and coronary artery calcification: a two-sample Mendelian randomization study"],"prefix":"10.1093","author":[{"given":"Liaoming","family":"He","sequence":"first","affiliation":[{"name":"National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College , Beilishi Road No. 167, Xicheng District, 100037 Beijing ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xieraili","family":"Tiemuerniyazi","sequence":"additional","affiliation":[{"name":"National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College , Beilishi Road No. 167, Xicheng District, 100037 Beijing ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ziang","family":"Yang","sequence":"additional","affiliation":[{"name":"National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College , Beilishi Road No. 167, Xicheng District, 100037 Beijing ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengkang","family":"Huang","sequence":"additional","affiliation":[{"name":"National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College , Beilishi Road No. 167, Xicheng District, 100037 Beijing ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lianxin","family":"Chen","sequence":"additional","affiliation":[{"name":"National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College , Beilishi Road No. 167, Xicheng District, 100037 Beijing ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifeng","family":"Nan","sequence":"additional","affiliation":[{"name":"National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College , Beilishi Road No. 167, Xicheng District, 100037 Beijing ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangwu","family":"Song","sequence":"additional","affiliation":[{"name":"National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College , Beilishi Road No. 167, Xicheng District, 100037 Beijing ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1157-8302","authenticated-orcid":false,"given":"Wei","family":"Feng","sequence":"additional","affiliation":[{"name":"National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College , Beilishi Road No. 167, Xicheng District, 100037 Beijing ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,10,14]]},"reference":[{"key":"2024102302244834700_zwae336-B1","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41575-021-00523-4","article-title":"Advancing the global public health agenda for NAFLD: a consensus statement","volume":"19","author":"Lazarus","year":"2022","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2024102302244834700_zwae336-B2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease\u2014meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"2024102302244834700_zwae336-B3","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.jhep.2008.06.018","article-title":"Increased overall mortality and liver-related mortality in non-alcoholic fatty liver disease","volume":"49","author":"Ong","year":"2008","journal-title":"J Hepatol"},{"key":"2024102302244834700_zwae336-B4","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1016\/j.cgh.2021.09.021","article-title":"A meta-analysis on the global prevalence, risk factors and screening of coronary heart disease in nonalcoholic fatty liver disease","volume":"20","author":"Toh","year":"2022","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2024102302244834700_zwae336-B5","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1001\/jama.2010.461","article-title":"Coronary artery calcium score and risk classification for coronary heart disease prediction","volume":"303","author":"Polonsky","year":"2010","journal-title":"JAMA"},{"key":"2024102302244834700_zwae336-B6","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1136\/gutjnl-2016-311854","article-title":"Non-alcoholic fatty liver disease and progression of coronary artery calcium score: a retrospective cohort study","volume":"66","author":"Sinn","year":"2017","journal-title":"Gut"},{"key":"2024102302244834700_zwae336-B7","doi-asserted-by":"crossref","first-page":"102938","DOI":"10.1016\/j.dsx.2023.102938","article-title":"Association between non-alcoholic fatty liver disease and coronary artery disease outcomes: a systematic review and meta-analysis","volume":"18","author":"Abosheaishaa","year":"2024","journal-title":"Diabetes Metab Syndr"},{"key":"2024102302244834700_zwae336-B8","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.jvs.2019.03.044","article-title":"The association between liver fat and systemic calcified atherosclerosis","volume":"71","author":"Koo","year":"2020","journal-title":"J Vasc Surg"},{"key":"2024102302244834700_zwae336-B9","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1161\/ATVBAHA.122.318661","article-title":"Comparative associations of nonalcoholic fatty liver disease and metabolic dysfunction-associated fatty liver disease with coronary artery calcification: a cross-sectional and longitudinal cohort study","volume":"43","author":"Sung","year":"2023","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2024102302244834700_zwae336-B10","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/j.jhep.2017.12.012","article-title":"Association between non-alcoholic fatty liver disease and subclinical coronary atherosclerosis: an observational cohort study","volume":"68","author":"Lee","year":"2018","journal-title":"J Hepatol"},{"key":"2024102302244834700_zwae336-B11","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/S2468-1253(21)00020-0","article-title":"Non-alcoholic fatty liver disease: a multisystem disease requiring a multidisciplinary and holistic approach","volume":"6","author":"Targher","year":"2021","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2024102302244834700_zwae336-B12","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1146\/annurev-genom-083117-021731","article-title":"Inferring causal relationships between risk factors and outcomes from genome-wide association study data","volume":"19","author":"Burgess","year":"2018","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"2024102302244834700_zwae336-B13","doi-asserted-by":"crossref","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":"2024102302244834700_zwae336-B14","doi-asserted-by":"crossref","first-page":"R89","DOI":"10.1093\/hmg\/ddu328","article-title":"Mendelian randomization: genetic anchors for causal inference in epidemiological studies","volume":"23","author":"Davey Smith","year":"2014","journal-title":"Hum Mol Genet"},{"key":"2024102302244834700_zwae336-B15","doi-asserted-by":"crossref","first-page":"761","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":"2024102302244834700_zwae336-B16","doi-asserted-by":"crossref","first-page":"508","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":"2024102302244834700_zwae336-B17","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/hep4.1805","article-title":"Genome-wide association study of NAFLD using electronic health records","volume":"6","author":"Fairfield","year":"2022","journal-title":"Hepatol Commun"},{"key":"2024102302244834700_zwae336-B18","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1038\/s41588-023-01518-4","article-title":"Multi-ancestry genome-wide study identifies effector genes and druggable pathways for coronary artery calcification","volume":"55","author":"Kavousi","year":"2023","journal-title":"Nat Genet"},{"key":"2024102302244834700_zwae336-B19","doi-asserted-by":"crossref","first-page":"100066","DOI":"10.1016\/j.xgen.2021.100066","article-title":"Machine learning enables new insights into genetic contributions to liver fat accumulation","volume":"1","author":"Haas","year":"2021","journal-title":"Cell Genom"},{"key":"2024102302244834700_zwae336-B20","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1093\/ije\/dyr036","article-title":"Avoiding bias from weak instruments in Mendelian randomization studies","volume":"40","author":"Burgess","year":"2011","journal-title":"Int J Epidemiol"},{"key":"2024102302244834700_zwae336-B21","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s10654-017-0255-x","article-title":"Interpreting findings from Mendelian randomization using the MR-Egger method","volume":"32","author":"Burgess","year":"2017","journal-title":"Eur J Epidemiol"},{"key":"2024102302244834700_zwae336-B22","doi-asserted-by":"crossref","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":"2024102302244834700_zwae336-B23","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement","volume":"73","author":"Eslam","year":"2020","journal-title":"J Hepatol"},{"key":"2024102302244834700_zwae336-B24","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1007\/s12072-023-10517-w","article-title":"Impact of metabolic factors on risk of cardiovascular disease in nondiabetic metabolic dysfunction-associated fatty liver disease","volume":"17","author":"Kang","year":"2023","journal-title":"Hepatol Int"},{"key":"2024102302244834700_zwae336-B25","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1111\/j.1572-0241.2008.02188.x","article-title":"Hepatic steatosis and subclinical cardiovascular disease in a cohort enriched for type 2 diabetes: the Diabetes Heart Study","volume":"103","author":"McKimmie","year":"2008","journal-title":"Am J Gastroenterol"},{"key":"2024102302244834700_zwae336-B26","doi-asserted-by":"crossref","first-page":"l5367","DOI":"10.1136\/bmj.l5367","article-title":"Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults","volume":"367","author":"Alexander","year":"2019","journal-title":"BMJ"},{"key":"2024102302244834700_zwae336-B27","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1093\/eurjpc\/zwab212","article-title":"Risk of cardiovascular events in patients with non-alcoholic fatty liver disease: a systematic review and meta-analysis","volume":"29","author":"Alon","year":"2022","journal-title":"Eur J Prev Cardiol"}],"container-title":["European Journal of Preventive Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eurjpc\/advance-article-pdf\/doi\/10.1093\/eurjpc\/zwae336\/59973174\/zwae336.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjpc\/advance-article-pdf\/doi\/10.1093\/eurjpc\/zwae336\/59973174\/zwae336.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T02:25:08Z","timestamp":1729650308000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjpc\/advance-article\/doi\/10.1093\/eurjpc\/zwae336\/7821070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,14]]},"references-count":27,"URL":"https:\/\/doi.org\/10.1093\/eurjpc\/zwae336","relation":{},"ISSN":["2047-4873","2047-4881"],"issn-type":[{"value":"2047-4873","type":"print"},{"value":"2047-4881","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,14]]},"article-number":"zwae336"}}