{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:53:20Z","timestamp":1787003600709,"version":"build-2736575974"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,12,6]],"date-time":"2023-12-06T00:00:00Z","timestamp":1701820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Fetuin-A acts as both an inhibitor of calcification and insulin signaling. Previous studies reported conflicting results on the association between fetuin-A and cardiometabolic diseases. We aim to provide further insights into the association between genetically predicted levels of fetuin-A and cardiometabolic diseases using a Mendelian randomization strategy. Genetic variants associated with fetuin-A and their effect sizes were obtained from previous genetic studies. A series of two-sample Mendelian randomization analyses in 412,444 unrelated individuals from the UK Biobank did not show evidence for an association of genetically predicted fetuin-A with any stroke, ischemic stroke, or myocardial infarction. We do find that increased levels of genetically predicted fetuin-A are associated with increased risk of type 2 diabetes (OR\u2009=\u20091.21, 95%CI 1.13\u20131.30,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u2009\u2009&lt;\u20090.01). Furthermore, genetically predicted fetuin-A increases the risk of coronary artery disease in individuals with type 2 diabetes, but we did not find evidence for an association between genetically predicted fetuin-A and coronary artery disease in those without type 2 diabetes (\n                    <jats:italic>P<\/jats:italic>\n                    for interaction\u2009=\u20090.03). One SD increase in genetically predicted fetuin-A decreases risk of myocardial infarction in women, but we do not find evidence for an association between genetically predicted fetuin-A and myocardial infarction in men (\n                    <jats:italic>P<\/jats:italic>\n                    for interaction\u2009=\u2009\u2009&lt;\u20090.01). Genetically predicted fetuin-A is associated with type 2 diabetes. Furthermore, type 2 diabetes status modifies the association of genetically predicted fetuin-A with coronary artery disease, indicating that fetuin-A increases risk in individuals with type 2 diabetes. Finally, higher genetically predicted fetuin-A reduces the risk of myocardial infarction in women, but we do not find evidence for an association between genetically predicted fetuin-A and myocardial infarction in men.\n                  <\/jats:p>","DOI":"10.1038\/s41598-023-48600-9","type":"journal-article","created":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T22:02:03Z","timestamp":1701813723000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Fetuin-A and its genetic association with cardiometabolic disease"],"prefix":"10.1038","volume":"13","author":[{"given":"Lawien","family":"Al Ali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yordi J.","family":"van de Vegte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Abdullah","family":"Said","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilde E.","family":"Groot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Hendriks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming Wai","family":"Yeung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik","family":"Lipsic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pim","family":"van der Harst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,12,6]]},"reference":[{"key":"48600_CR1","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1172\/JCI17202","volume":"112","author":"C Sch\u00e4fer","year":"2003","unstructured":"Sch\u00e4fer, C. et al. The serum protein \u03b12-Heremans-Schmid glycoprotein\/fetuin-A is a systemically acting inhibitor of ectopic calcification. J. Clin. Invest. 112, 357\u2013366 (2003).","journal-title":"J. Clin. Invest."},{"key":"48600_CR2","first-page":"1445","volume":"7","author":"PR Srinivas","year":"1993","unstructured":"Srinivas, P. R. et al. Serum \u03b12-HS-glycoprotein is an inhibitor of the human insulin receptor at the tyrosine kinase level. Mol. Endocrinol. 7, 1445\u20131455 (1993).","journal-title":"Mol. Endocrinol."},{"key":"48600_CR3","doi-asserted-by":"publisher","first-page":"853","DOI":"10.2337\/diacare.29.04.06.dc05-1938","volume":"29","author":"N Stefan","year":"2006","unstructured":"Stefan, N. et al. \u03b12-Heremans-Schmid glycoprotein\/fetuin-A is associated with insulin resistance and fat accumulation in the liver in humans. 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