{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:00:02Z","timestamp":1787029202325,"version":"build-2736575974"},"reference-count":29,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T00:00:00Z","timestamp":1733443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jiangsu Province Capability Improvement Project through Science, Technology and Education","award":["ZDXK202248"],"award-info":[{"award-number":["ZDXK202248"]}]},{"name":"Jiangsu Province Capability Improvement Project through Science, Technology and Education","award":["SYH-32099-0119(2024023)"],"award-info":[{"award-number":["SYH-32099-0119(2024023)"]}]},{"name":"Jiangsu Medical Association Medical Research Project of Health Management","award":["ZDXK202248"],"award-info":[{"award-number":["ZDXK202248"]}]},{"name":"Jiangsu Medical Association Medical Research Project of Health Management","award":["SYH-32099-0119(2024023)"],"award-info":[{"award-number":["SYH-32099-0119(2024023)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Whether an increased genetic risk of steatotic liver disease (SLD) can be offset by maintaining a healthy weight remains unknown. We aimed to clarify the associations among the body mass index (BMI) and its change patterns with SLD and assess whether genetic susceptibility can modify these associations in Chinese people. Methods: A total of 10,091 and 6124 participants from the Health Omics Preventive Examination (HOPE) Program were enrolled in cross-sectional and follow-up analyses, respectively. BMI change patterns were defined according to the BMI at baseline and the last follow-up visit. Genetic risk was estimated using the polygenic risk score (PRS) derived from variants in PNPLA3, TM6SF2, MBOAT7, and GCKR. Data were analyzed using logistic regression models and Cox proportional-hazards models. Results: The analyses of the BMI and genetic risk simultaneously showed a dose\u2013response association with the risk of SLD (p-trend &lt;\u20090.001). Significant interactions between BMI and PRS were found for alanine aminotransferase (ALT) elevation (p = 0.007) and aspartate aminotransferase (AST) elevation (p &lt;\u20090.001). Weight loss led to a 71%, 60%, and 67% lower risk of SLD, ALT elevation, and AST elevation, compared with stable overweight\/obesity. A significant interaction between the genetic risk and BMI change patterns in ALT elevation was observed (p = 0.008). The absolute risk reductions associated with weight loss were greater for participants at a high genetic risk (26.60, 12.29, and 9.31 per 100 person years for SLD, ALT elevation, and AST elevation, respectively). Conclusions: Maintaining a healthy weight reduces the liver injury risk among all individuals, and the risk reduction is greater among the subset with a high genetic risk of SLD.<\/jats:p>","DOI":"10.3390\/nu16234212","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T03:44:47Z","timestamp":1733456687000},"page":"4212","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic Risk, BMI Status, BMI Change Patterns, and the Risk of Steatotic Liver Disease and Liver Enzyme Elevation in Chinese Adults"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6592-3674","authenticated-orcid":false,"given":"Juan","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maojie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Fan","sequence":"additional","affiliation":[{"name":"Health Management Center, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou 234099, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6735-0027","authenticated-orcid":false,"given":"Chengxiao","family":"Yu","sequence":"additional","affiliation":[{"name":"Health Management Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Health Management Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1016\/S0140-6736(20)32511-3","article-title":"Non-alcoholic fatty liver disease","volume":"397","author":"Powell","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1016\/j.jhep.2023.08.030","article-title":"Endocrine aspects of metabolic dysfunction-associated steatotic liver disease (MASLD): Beyond insulin resistance","volume":"79","author":"Hutchison","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1111\/obr.12407","article-title":"Obesity is an independent risk factor for non-alcoholic fatty liver disease: Evidence from a meta-analysis of 21 cohort studies","volume":"17","author":"Li","year":"2016","journal-title":"Obes. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1111\/liv.13603","article-title":"Body mass index trajectories in young adulthood predict non-alcoholic fatty liver disease in middle age: The CARDIA cohort study","volume":"38","author":"VanWagner","year":"2018","journal-title":"Liver Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1053\/j.gastro.2015.04.005","article-title":"Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis","volume":"149","author":"Friedman","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e583","DOI":"10.1016\/j.cgh.2021.04.037","article-title":"Weight Change and the Development of Nonalcoholic Fatty Liver Disease in Metabolically Healthy Overweight Individuals","volume":"20","author":"Cho","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"733","DOI":"10.14309\/ajg.0000000000001030","article-title":"Impact of Body Weight Gain on the Incidence of Nonalcoholic Fatty Liver Disease in Nonobese Japanese Individuals","volume":"116","author":"Yamada","year":"2021","journal-title":"Am. J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S2213-8587(18)30154-2","article-title":"Non-alcoholic fatty liver disease: Causes, diagnosis, cardiometabolic consequences, and treatment strategies","volume":"7","author":"Stefan","year":"2019","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1053\/j.gastro.2009.03.065","article-title":"Heritability of nonalcoholic fatty liver disease","volume":"137","author":"Brouwers","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1038\/s41588-023-01497-6","article-title":"Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease","volume":"55","author":"Chen","year":"2023","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.cgh.2021.05.056","article-title":"A Polygenic Risk Score to Refine Risk Stratification and Prediction for Severe Liver Disease by Clinical Fibrosis Scores","volume":"20","author":"Tavaglione","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1111\/liv.15613","article-title":"An adult-based genetic risk score for liver fat associates with liver and plasma lipid traits in children and adolescents","volume":"43","author":"Huang","year":"2023","journal-title":"Liver Int."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1038\/pr.2016.139","article-title":"Association of MBOAT7 gene variant with plasma ALT levels in children: The PANIC study","volume":"80","author":"Viitasalo","year":"2016","journal-title":"Pediatr. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/ng.3855","article-title":"Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci","volume":"49","author":"Stender","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_15","first-page":"1","article-title":"The guidelines for prevention and control of overweight and obesity in Chinese adults","volume":"17","author":"Chen","year":"2004","journal-title":"Biomed. Environ. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1016\/j.jhep.2023.06.003","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"79","author":"Rinella","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.acra.2012.02.022","article-title":"Computed tomography scans in the evaluation of fatty liver disease in a population based study: The multi-ethnic study of atherosclerosis","volume":"19","author":"Zeb","year":"2012","journal-title":"Acad. Radiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/ajg.2016.517","article-title":"ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries","volume":"112","author":"Kwo","year":"2017","journal-title":"Am. J. Gastroenterol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1002\/hep.28390","article-title":"Noninvasive fatty liver markers predict liver disease mortality in the U.S. population","volume":"63","author":"Ruhl","year":"2016","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1016\/j.jhep.2018.08.011","article-title":"Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease","volume":"69","author":"Wong","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e538","DOI":"10.1016\/j.cgh.2021.03.047","article-title":"Association of Weight Changes With Changes in Histological Features and Blood Markers in Nonalcoholic Steatohepatitis","volume":"20","author":"Koutoukidis","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Di Costanzo, A., Belardinilli, F., Bailetti, D., Sponziello, M., D\u2019Erasmo, L., Polimeni, L., Baratta, F., Pastori, D., Ceci, F., and Montali, A. (2018). Evaluation of Polygenic Determinants of Non-Alcoholic Fatty Liver Disease (NAFLD) By a Candidate Genes Resequencing Strategy. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-21939-0"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.jhep.2020.11.024","article-title":"Non-invasive stratification of hepatocellular carcinoma risk in non-alcoholic fatty liver using polygenic risk scores","volume":"74","author":"Bianco","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2310","DOI":"10.1002\/hep4.1976","article-title":"NAFLD polygenic risk score and risk of hepatocellular carcinoma in an East Asian population","volume":"6","author":"Thomas","year":"2022","journal-title":"Hepatol. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1053\/j.gastro.2018.03.038","article-title":"Improved Diet Quality Associates With Reduction in Liver Fat, Particularly in Individuals With High Genetic Risk Scores for Nonalcoholic Fatty Liver Disease","volume":"155","author":"Ma","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1002\/hep.31238","article-title":"Combined Effect of PNPLA3, TM6SF2, and HSD17B13 Variants on Risk of Cirrhosis and Hepatocellular Carcinoma in the General Population","volume":"72","author":"Richardson","year":"2020","journal-title":"Hepatology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1002\/hep4.1932","article-title":"Interactions of physical activity, muscular fitness, adiposity, and genetic risk for NAFLD","volume":"6","author":"Schnurr","year":"2022","journal-title":"Hepatol. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1053\/j.gastro.2020.12.011","article-title":"Association of Genetic Variation With Cirrhosis: A Multi-Trait Genome-Wide Association and Gene-Environment Interaction Study","volume":"160","author":"Emdin","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3771","DOI":"10.1038\/s41467-022-30931-2","article-title":"Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots","volume":"13","author":"Agrawal","year":"2022","journal-title":"Nat. Commun."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/23\/4212\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:48:13Z","timestamp":1760114893000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/23\/4212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,6]]},"references-count":29,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["nu16234212"],"URL":"https:\/\/doi.org\/10.3390\/nu16234212","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,6]]}}}