{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:21:11Z","timestamp":1790659271730,"version":"4.1.0"},"reference-count":45,"publisher":"Georg Thieme Verlag KG","issue":"05","funder":[{"name":"Science Foundation of Health Commission of\n                        Wuxi."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Studies have covered a possible relevance between fibroblast growth factor 21\n                        (FGF21) and obesity-related metabolic complications and cardiovascular\n                        disease (CVD). Nevertheless, whether FGF21 is a causative factor in these\n                        diseases is not known. Using a bidirectional, two-sample Mendelian\n                        randomization (MR) approach, this study sought to establish a causal\n                        relationship between FGF21 and seven metabolic diseases and six CVDs. <\/jats:p><jats:p>A large-scale meta-analysis dataset of genome-wide association studies (GWAS)\n                        was analyzed to generate summary-level statistics for FGF21. The diseases we\n                        studied included non-alcoholic fatty liver disease (NAFLD), obesity, type 2\n                        diabetes (T2DM), hypertension, gestational diabetes (GDM), gestational\n                        hypertension (GHTN), pre-eclampsia or eclampsia (PE), atherosclerosis,\n                        cardiomyopathy (CMP), coronary heart disease (CHD), coronary\n                        atherosclerosis, heart failure (HF), myocardial infarction (MI) and the\n                        corresponding summary GAWS data were retrieved from the FinnGen Biobank and\n                        IEU Open GWAS Project database. The inverse variance-weighted (IVW)\n                        algorithm was the primary approach utilized for the MR analysis. The\n                        MR-Egger regression and MR-PRESSO tests were implemented to evaluate\n                        horizontal pleiotropy. The heterogeneity of instrumental variables was\n                        subsequently assessed utilizing Cochran\u02bcs Q statistics.<\/jats:p><jats:p>When diseases are used as exposures, MR analysis results of the IVW method\n                        indicated that NAFLD (Beta=\u2212\u20090.047, 95% CI=\u2212\u20090.08 to \u2212\u20090.014; p=0.006),\n                        obesity (Beta=0.087, 95% CI=0.021\u20130.153; p=0.009), T2DM (Beta=0.071, 95%\n                        CI=0.037\u20130.106; p&lt;0.001) correlated causally with FGF21. Nevertheless,\n                        FGF21 was not causally related to the remaining metabolic diseases and CVDs,\n                        according to the results of the MR analysis (p&gt;0.05). It was demonstrated\n                        that the aforementioned results were robust and devoid of pleiotropy.<\/jats:p><jats:p>Our study supports a causal association between NAFLD, obesity, and T2DM with\n                        FGF21. No substantial evidence exists to establish a causal relationship\n                        between FGF21 and other diseases. This study provides opportunities for the\n                        early prevention and innovative therapy of NAFLD, obesity, and T2DM.<\/jats:p>","DOI":"10.1055\/a-2549-6889","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T23:16:31Z","timestamp":1744931791000},"page":"259-267","source":"Crossref","is-referenced-by-count":4,"title":["Association of FGF21 with Metabolic and Cardiovascular Diseases: A\n                    Mendelian Randomization Analysis"],"prefix":"10.1055","volume":"133","author":[{"given":"Qingwen","family":"He","sequence":"first","affiliation":[{"name":"Affiliated Women\u02bcs Hospital of Jiangnan University,\n                    Wuxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuguang","family":"Li","sequence":"first","affiliation":[{"name":"Affiliated Women\u02bcs Hospital of Jiangnan University,\n                    Wuxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renqiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Affiliated Women\u02bcs Hospital of Jiangnan University,\n                    Wuxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Affiliated Women\u02bcs Hospital of Jiangnan University,\n                    Wuxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"155166","DOI":"10.1016\/j.metabol.2022.155166","article-title":"Fibroblast growth factor 21: A \"rheostat\" for metabolic\n                    regulation?","volume":"130","author":"Q Y 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lipotoxicity and macrophage activation to\n                    attenuate fibrogenesis in nonalcoholic steatohepatitis","volume":"12","author":"C Liu","year":"2023","journal-title":"Elife"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e50524","DOI":"10.7759\/cureus.50524","article-title":"Fibroblast growth factor 21: A more effective biomarker than free fatty acids\n                    and other insulin sensitivity measures for predicting non-alcoholic fatty liver\n                    disease in Saudi Arabian type 2 diabetes patients","volume":"15","author":"S Bahijri","year":"2023","journal-title":"Cureus"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"601290","DOI":"10.3389\/fendo.2020.601290","article-title":"FGF21: An emerging therapeutic target for non-alcoholic steatohepatitis and\n                    related metabolic diseases","volume":"1","author":"E J Tillman","year":"2020","journal-title":"Front Endocrinol 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Fisher","year":"2010","journal-title":"Diabetes"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"153994","DOI":"10.1016\/j.metabol.2019.153994","article-title":"Fibroblast growth factor 21 in non-alcoholic fatty liver disease","volume":"101","author":"B Tucker","year":"2019","journal-title":"Metabolism"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1172\/JCI23606","article-title":"FGF-21 as a novel metabolic regulator","volume":"115","author":"A Kharitonenkov","year":"2005","journal-title":"J Clin Invest"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/s41574-020-0386-0","article-title":"The therapeutic potential of FGF21 in metabolic diseases: From bench to\n                    clinic","volume":"16","author":"L Geng","year":"2020","journal-title":"Nat Rev Endocrinol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1055\/a-0879-2968","article-title":"Circulating FGF21 levels in human 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Xu","year":"2013","journal-title":"PLoS One"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1111\/joim.13467","article-title":"Ambient air pollution and cardiovascular diseases: An umbrella review of\n                    systematic reviews and meta-analyses","volume":"291","author":"J de Bont","year":"2022","journal-title":"J Intern Med"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"66","DOI":"10.7150\/ijbs.73936","article-title":"Targeting FGF21 in cardiovascular and metabolic diseases: From mechanism to\n                    medicine","volume":"19","author":"H Tan","year":"2023","journal-title":"Int J Biol Sci"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"e005344","DOI":"10.1161\/JAHA.116.005344","article-title":"Role of circulating fibroblast growth factor 21 measurement in primary\n                    prevention of coronary heart disease among Chinese patients with type 2 diabetes\n                    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