{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T23:07:37Z","timestamp":1776985657055,"version":"3.51.4"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"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><jats:p>With the aging of the population, sarcopenia has become more common. Studies have shown a broad association between liver disease and sarcopenia. However, this link remains unclear. Our study explored the link between NAFLD and sarcopenia and predicting the pathogenesis. To begin, we investigated the causal relationship and genetic correlation between them using MR and LDSC. Second, each GWAS was annotated by MAGMA. The annotated genes were analyzed for pleiotropy using the PLACO approach. Finally, functional analysis was conducted on the identified pleiotropic genes. We observed a significant genetic correlation between NAFLD and sarcopenia. Subsequently, we conducted gene-level pleiotropy analysis using PLACO and identified a total of 153 genes with pleiotropic effects. Functional analysis revealed enrichment of these genes in various tissues, including pancreas, liver, heart, blood, brain, and muscle, with involvement in cellular regulation, intracellular function, and antigen response. Moreover, our MR analysis provided evidence of a causal relationship between NAFLD and sarcopenia. Our study has discovered the genetic and causal relationships between NAFLD and sarcopenia, providing further insights into their pathophysiological mechanisms. The identification of pleiotropic genes also offers potential targets for future drug therapies aimed at controlling or treating NAFLD and sarcopenia.<\/jats:p>","DOI":"10.1038\/s41598-024-53112-1","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T17:02:33Z","timestamp":1706806953000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Effects of nonalcoholic fatty liver disease on sarcopenia: evidence from genetic methods"],"prefix":"10.1038","volume":"14","author":[{"given":"Jiaqin","family":"Yuan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinglin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lipeng","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,2,1]]},"reference":[{"issue":"5 Suppl","key":"53112_CR1","doi-asserted-by":"publisher","first-page":"990S","DOI":"10.1093\/jn\/127.5.990S","volume":"127","author":"IH Rosenberg","year":"1997","unstructured":"Rosenberg, I. H. Sarcopenia: origins and clinical relevance. J. Nutr. 127(5 Suppl), 990S-991S. https:\/\/doi.org\/10.1093\/jn\/127.5.990S (1997).","journal-title":"J. Nutr."},{"issue":"5","key":"53112_CR2","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.1002\/hep.26716","volume":"59","author":"HC Hong","year":"2014","unstructured":"Hong, H. C. et al. Relationship between sarcopenia and nonalcoholic fatty liver disease: the Korean Sarcopenic Obesity Study. Hepatology. 59(5), 1772\u20131778. https:\/\/doi.org\/10.1002\/hep.26716 (2014).","journal-title":"Hepatology."},{"issue":"9","key":"53112_CR3","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1097\/MEG.0000000000001397","volume":"31","author":"K Wijarnpreecha","year":"2019","unstructured":"Wijarnpreecha, K., Kim, D., Raymond, P., Scribani, M. & Ahmed, A. Associations between sarcopenia and nonalcoholic fatty liver disease and advanced fibrosis in the USA. Eur. J. Gastroenterol. Hepatol. 31(9), 1121\u20131128. https:\/\/doi.org\/10.1097\/MEG.0000000000001397 (2019).","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"issue":"1","key":"53112_CR4","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1093\/ageing\/afy169","volume":"48","author":"AJ Cruz-Jentoft","year":"2019","unstructured":"Cruz-Jentoft, A. J. et al. Sarcopenia: Revised European consensus on definition and diagnosis. Age Ageing. 48(1), 16\u201331. https:\/\/doi.org\/10.1093\/ageing\/afy169 (2019).","journal-title":"Age Ageing."},{"issue":"22","key":"53112_CR5","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.1001\/jama.2015.5370","volume":"313","author":"ME Rinella","year":"2015","unstructured":"Rinella, M. E. Nonalcoholic fatty liver disease: A systematic review. JAMA. 313(22), 2263\u20132273. https:\/\/doi.org\/10.1001\/jama.2015.5370 (2015).","journal-title":"JAMA."},{"issue":"1","key":"53112_CR6","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/hep.28431","volume":"64","author":"ZM Younossi","year":"2016","unstructured":"Younossi, Z. M. et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 64(1), 73\u201384. https:\/\/doi.org\/10.1002\/hep.28431 (2016).","journal-title":"Hepatology."},{"issue":"7","key":"53112_CR7","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1007\/s00125-017-4264-9","volume":"60","author":"E Blond","year":"2017","unstructured":"Blond, E. et al. EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease in severely obese people: Do they lead to over-referral?. Diabetologia. 60(7), 1218\u20131222. https:\/\/doi.org\/10.1007\/s00125-017-4264-9 (2017).","journal-title":"Diabetologia."},{"issue":"1","key":"53112_CR8","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.jhep.2016.08.019","volume":"66","author":"BK Koo","year":"2017","unstructured":"Koo, B. K. et al. Sarcopenia is an independent risk factor for non-alcoholic steatohepatitis and significant fibrosis. J. Hepatol. 66(1), 123\u2013131. https:\/\/doi.org\/10.1016\/j.jhep.2016.08.019 (2017).","journal-title":"J. Hepatol."},{"issue":"3","key":"53112_CR9","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1002\/hep.28376","volume":"63","author":"YH Lee","year":"2016","unstructured":"Lee, Y. H. et al. Sarcopenia is associated with significant liver fibrosis independently of obesity and insulin resistance in nonalcoholic fatty liver disease: Nationwide surveys (KNHANES 2008\u20132011). Hepatology. 63(3), 776\u2013786. https:\/\/doi.org\/10.1002\/hep.28376 (2016).","journal-title":"Hepatology."},{"key":"53112_CR10","doi-asserted-by":"publisher","first-page":"588","DOI":"10.3389\/fendo.2018.00588","volume":"9","author":"H Takahashi","year":"2018","unstructured":"Takahashi, H., Kotani, K., Tanaka, K., Egucih, Y. & Anzai, K. Therapeutic approaches to nonalcoholic fatty liver disease: Exercise intervention and related mechanisms. Front. Endocrinol. (Lausanne). 9, 588. https:\/\/doi.org\/10.3389\/fendo.2018.00588 (2018).","journal-title":"Front. Endocrinol. (Lausanne)."},{"issue":"11","key":"53112_CR11","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1038\/ng.3406","volume":"47","author":"B Bulik-Sullivan","year":"2015","unstructured":"Bulik-Sullivan, B. et al. An atlas of genetic correlations across human diseases and traits. Nat. Genet. 47(11), 1236\u20131241. https:\/\/doi.org\/10.1038\/ng.3406 (2015).","journal-title":"Nat. Genet."},{"issue":"4","key":"53112_CR12","doi-asserted-by":"publisher","first-page":"e1004219","DOI":"10.1371\/journal.pcbi.1004219","volume":"11","author":"CA de Leeuw","year":"2015","unstructured":"de Leeuw, C. A., Mooij, J. M., Heskes, T. & Posthuma, D. MAGMA: generalized gene-set analysis of GWAS data. PLoS Comput. Biol. 11(4), e1004219. https:\/\/doi.org\/10.1371\/journal.pcbi.1004219 (2015).","journal-title":"PLoS Comput. Biol."},{"issue":"12","key":"53112_CR13","doi-asserted-by":"publisher","first-page":"e1009218","DOI":"10.1371\/journal.pgen.1009218","volume":"16","author":"D Ray","year":"2020","unstructured":"Ray, D. & Chatterjee, N. A powerful method for pleiotropic analysis under composite null hypothesis identifies novel shared loci between Type 2 Diabetes and Prostate Cancer. PLoS Genet. 16(12), e1009218. https:\/\/doi.org\/10.1371\/journal.pgen.1009218 (2020).","journal-title":"PLoS Genet."},{"issue":"2","key":"53112_CR14","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1002\/hep4.1805","volume":"6","author":"CJ Fairfield","year":"2022","unstructured":"Fairfield, C. J. et al. Genome-wide association study of NAFLD using electronic health records. Hepatol. Commun. 6(2), 297\u2013308. https:\/\/doi.org\/10.1002\/hep4.1805 (2022).","journal-title":"Hepatol. Commun."},{"issue":"1","key":"53112_CR15","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1038\/s42003-020-01334-0","volume":"3","author":"YF Pei","year":"2020","unstructured":"Pei, Y. F. et al. The genetic architecture of appendicular lean mass characterized by association analysis in the UK Biobank study. Commun. Biol. 3(1), 608. https:\/\/doi.org\/10.1038\/s42003-020-01334-0 (2020).","journal-title":"Commun. Biol."},{"issue":"5","key":"53112_CR16","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.1177\/0962280215597579","volume":"26","author":"S Burgess","year":"2017","unstructured":"Burgess, S., Small, D. S. & Thompson, S. G. A review of instrumental variable estimators for Mendelian randomization. Stat. Methods Med. Res. 26(5), 2333\u20132355. https:\/\/doi.org\/10.1177\/0962280215597579 (2017).","journal-title":"Stat. Methods Med. Res."},{"key":"53112_CR17","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k601","volume":"362","author":"NM Davies","year":"2018","unstructured":"Davies, N. M., Holmes, M. V. & Davey, S. G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ. 362, k601. https:\/\/doi.org\/10.1136\/bmj.k601 (2018).","journal-title":"BMJ."},{"issue":"5","key":"53112_CR18","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","volume":"50","author":"M Verbanck","year":"2018","unstructured":"Verbanck, M., Chen, C. Y., Neale, B. & Do, R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat. Genet. 50(5), 693\u2013698. https:\/\/doi.org\/10.1038\/s41588-018-0099-7 (2018).","journal-title":"Nat. Genet."},{"issue":"7571","key":"53112_CR19","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","volume":"526","author":"A Auton","year":"2015","unstructured":"Auton, A. et al. A global reference for human genetic variation. Nature. 526(7571), 68\u201374. https:\/\/doi.org\/10.1038\/nature15393 (2015).","journal-title":"Nature."},{"issue":"1","key":"53112_CR20","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1186\/s12916-021-02186-z","volume":"19","author":"H Lu","year":"2021","unstructured":"Lu, H. et al. A comprehensive gene-centric pleiotropic association analysis for 14 psychiatric disorders with GWAS summary statistics. BMC Med. 19(1), 314. https:\/\/doi.org\/10.1186\/s12916-021-02186-z (2021).","journal-title":"BMC Med."},{"issue":"4","key":"53112_CR21","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1111\/biom.13073","volume":"75","author":"YT Huang","year":"2019","unstructured":"Huang, Y. T. Variance component tests of multivariate mediation effects under composite null hypotheses. Biometrics. 75(4), 1191\u20131204. https:\/\/doi.org\/10.1111\/biom.13073 (2019).","journal-title":"Biometrics."},{"issue":"1","key":"53112_CR22","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.1038\/s41467-017-01261-5","volume":"8","author":"K Watanabe","year":"2017","unstructured":"Watanabe, K., Taskesen, E., van Bochoven, A. & Posthuma, D. Functional mapping and annotation of genetic associations with FUMA. Nat. Commun. 8(1), 1826. https:\/\/doi.org\/10.1038\/s41467-017-01261-5 (2017).","journal-title":"Nat. Commun."},{"key":"53112_CR23","doi-asserted-by":"publisher","unstructured":"GTEx Consortium. The Genotype-Tissue Expression (GTEx) project. Nat Genet. 2013;45(6):580\u2013585. https:\/\/doi.org\/10.1038\/ng.2653","DOI":"10.1038\/ng.2653"},{"issue":"W1","key":"53112_CR24","doi-asserted-by":"publisher","first-page":"W216","DOI":"10.1093\/nar\/gkac194","volume":"50","author":"BT Sherman","year":"2022","unstructured":"Sherman, B. T. et al. DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 50(W1), W216\u2013W221. https:\/\/doi.org\/10.1093\/nar\/gkac194 (2022).","journal-title":"Nucleic Acids Res."},{"issue":"6","key":"53112_CR25","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.3390\/diagnostics11061061","volume":"11","author":"MK Kang","year":"2021","unstructured":"Kang, M. K. et al. Association of skeletal muscle and adipose tissue distribution with histologic severity of non-alcoholic fatty liver. Diagnostics (Basel). 11(6), 1061. https:\/\/doi.org\/10.3390\/diagnostics11061061 (2021).","journal-title":"Diagnostics (Basel)."},{"key":"53112_CR26","doi-asserted-by":"publisher","unstructured":"Issa, D., Alkhouri, N., Tsien, C., et al. Presence of sarcopenia (muscle wasting) in patients with nonalcoholic steatohepatitis [published correction appears in Hepatology. 2015 Oct;62(4):1330]. Hepatology. 2014;60(1):428\u2013429. https:\/\/doi.org\/10.1002\/hep.26908","DOI":"10.1002\/hep.26908"},{"issue":"4","key":"53112_CR27","doi-asserted-by":"publisher","first-page":"278","DOI":"10.4093\/dmj.2013.37.4.278","volume":"37","author":"JS Moon","year":"2013","unstructured":"Moon, J. S., Yoon, J. S., Won, K. C. & Lee, H. W. The role of skeletal muscle in development of nonalcoholic Fatty liver disease. Diabetes Metab. J. 37(4), 278\u2013285. https:\/\/doi.org\/10.4093\/dmj.2013.37.4.278 (2013).","journal-title":"Diabetes Metab. J."},{"issue":"2","key":"53112_CR28","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/j.jhep.2015.02.051","volume":"63","author":"YH Lee","year":"2015","unstructured":"Lee, Y. H. et al. Sarcopaenia is associated with NAFLD independently of obesity and insulin resistance: Nationwide surveys (KNHANES 2008\u20132011). J. Hepatol. 63(2), 486\u2013493. https:\/\/doi.org\/10.1016\/j.jhep.2015.02.051 (2015).","journal-title":"J. Hepatol."},{"issue":"4","key":"53112_CR29","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1111\/apt.13889","volume":"45","author":"S Petta","year":"2017","unstructured":"Petta, S. et al. Sarcopenia is associated with severe liver fibrosis in patients with non-alcoholic fatty liver disease. Aliment. Pharmacol. Ther. 45(4), 510\u2013518. https:\/\/doi.org\/10.1111\/apt.13889 (2017).","journal-title":"Aliment. Pharmacol. Ther."},{"issue":"1","key":"53112_CR30","doi-asserted-by":"publisher","first-page":"15647","DOI":"10.1038\/s41598-021-95108-1","volume":"11","author":"X Sun","year":"2021","unstructured":"Sun, X., Liu, Z., Chen, F. & Du, T. Sarcopenia modifies the associations of nonalcoholic fatty liver disease with all-cause and cardiovascular mortality among older adults. Sci. Rep. 11(1), 15647. https:\/\/doi.org\/10.1038\/s41598-021-95108-1 (2021).","journal-title":"Sci. Rep."},{"issue":"11","key":"53112_CR31","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.2522\/ptj.20080018","volume":"88","author":"LP Turcotte","year":"2008","unstructured":"Turcotte, L. P. & Fisher, J. S. Skeletal muscle insulin resistance: Roles of fatty acid metabolism and exercise. Phys. Ther. 88(11), 1279\u20131296. https:\/\/doi.org\/10.2522\/ptj.20080018 (2008).","journal-title":"Phys. Ther."},{"issue":"6","key":"53112_CR32","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.1002\/hep.29420","volume":"66","author":"RA Bhanji","year":"2017","unstructured":"Bhanji, R. A., Narayanan, P., Allen, A. M., Malhi, H. & Watt, K. D. Sarcopenia in hiding: The risk and consequence of underestimating muscle dysfunction in nonalcoholic steatohepatitis. Hepatology. 66(6), 2055\u20132065. https:\/\/doi.org\/10.1002\/hep.29420 (2017).","journal-title":"Hepatology."},{"issue":"1","key":"53112_CR33","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/s41419-020-03353-5","volume":"12","author":"T Kurosawa","year":"2021","unstructured":"Kurosawa, T. et al. Liver fibrosis-induced muscle atrophy is mediated by elevated levels of circulating TNF\u03b1. Cell Death Dis. 12(1), 11. https:\/\/doi.org\/10.1038\/s41419-020-03353-5 (2021).","journal-title":"Cell Death Dis."},{"key":"53112_CR34","doi-asserted-by":"publisher","first-page":"156","DOI":"10.3389\/fnagi.2014.00156","volume":"6","author":"F Sanchis-Gomar","year":"2014","unstructured":"Sanchis-Gomar, F., Pareja-Galeano, H., Mayero, S., Perez-Quilis, C. & Lucia, A. New molecular targets and lifestyle interventions to delay aging sarcopenia. Front. Aging Neurosci. 6, 156. https:\/\/doi.org\/10.3389\/fnagi.2014.00156 (2014).","journal-title":"Front. Aging Neurosci."},{"issue":"9","key":"53112_CR35","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1007\/s00125-009-1430-8","volume":"52","author":"S Fujita","year":"2009","unstructured":"Fujita, S., Glynn, E. L., Timmerman, K. L., Rasmussen, B. B. & Volpi, E. Supraphysiological hyperinsulinaemia is necessary to stimulate skeletal muscle protein anabolism in older adults: Evidence of a true age-related insulin resistance of muscle protein metabolism. Diabetologia. 52(9), 1889\u20131898. https:\/\/doi.org\/10.1007\/s00125-009-1430-8 (2009).","journal-title":"Diabetologia."},{"key":"53112_CR36","doi-asserted-by":"publisher","first-page":"117862641984217","DOI":"10.1177\/1178626419842176","volume":"12","author":"MS Lewitt","year":"2019","unstructured":"Lewitt, M. S. & Boyd, G. W. The role of insulin-like growth factors and insulin-like growth factor-binding proteins in the nervous system. Biochem. Insights. 12, 1178626419842176. https:\/\/doi.org\/10.1177\/1178626419842176 (2019).","journal-title":"Biochem. Insights."},{"issue":"1","key":"53112_CR37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0145811","volume":"11","author":"E Poggiogalle","year":"2016","unstructured":"Poggiogalle, E. et al. Fatty liver index associates with relative Sarcopenia and GH\/ IGF- 1 status in obese subjects. PLoS One. 11(1), e0145811. https:\/\/doi.org\/10.1371\/journal.pone.0145811 (2016).","journal-title":"PLoS One."},{"issue":"2","key":"53112_CR38","doi-asserted-by":"publisher","first-page":"E304","DOI":"10.1210\/jc.2012-3290","volume":"98","author":"ML Hribal","year":"2013","unstructured":"Hribal, M. L. et al. Insulin-like growth factor-I, inflammatory proteins, and fibrosis in subjects with nonalcoholic fatty liver disease. J. Clin. Endocrinol. Metab. 98(2), E304\u2013E308. https:\/\/doi.org\/10.1210\/jc.2012-3290 (2013).","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-53112-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-53112-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-53112-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,4]],"date-time":"2024-02-04T20:03:31Z","timestamp":1707077011000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-53112-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,1]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["53112"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-53112-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,1]]},"assertion":[{"value":"23 August 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"2709"}}