ArticleJournal of translational medicine2024
Polygenic risk score of metabolic dysfunction-associated steatotic liver disease amplifies the health impact on severe liver disease and metabolism-related outcomes.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Genetic Variants in Liver Cirrhosis: Classifications, Mechanisms, and Implications for Clinical Practice.Journal of personalized medicine · 2026Review
- Proteomic signature of metabolic dysfunction-associated steatotic liver disease and risk of atherosclerotic cardiovascular disease.Cardiovascular diabetology · 2025Article
- Metabolomic characterization of frailty identifies subtype-specific management strategies.NPJ digital medicine · 2025Article
- Genetic predeterminants and recent advancements in steatotic liver disease: A roadmap toward precision hepatology.World journal of hepatology · 2025Review
- Unraveling the Role of BAG3 in Hepatic Fibrosis: Genetic and Biomarker Insights in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).International journal of molecular sciences · 2025Article
- PRKAA2 mediates the pathogenesis of metabolic dysfunction-associated steatotic liver disease via PI3K/AKT signaling pathway.Human genomics · 2025Article
- GCKR Polymorphisms Increase the Risks of Low Bone Mineral Density in Young and Non-Obese Patients With MASLD and Hyperuricemia.The Kaohsiung journal of medical sciences · 2025Article
- Polygenic Risk Score for Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis: A Narrative Review.International journal of molecular sciences · 2025Review
- Review
- Genetic Risk Factors for Metabolic Dysfunction-Associated Steatotic Liver Disease.Gut and liver · 2025Review
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Authors and funding
14 authors.
Funding
Abstract
backgroundAlthough the inherited risk factors associated with fatty liver disease are well understood, little is known about the genetic background of metabolic dysfunction-associated steatotic liver disease (MASLD) and its related health impacts. Compared to non-alcoholic fatty liver disease (NAFLD), MASLD presents significantly distinct diagnostic criteria, and epidemiological and clinical features, but the related genetic variants are yet to be investigated. Therefore, we conducted this study to assess the genetic background of MASLD and interactions between MASLD-related genetic variants and metabolism-related outcomes.
methodsParticipants from the UK Biobank were grouped into discovery and replication cohorts for an MASLD genome-wide association study (GWAS), and base and target cohorts for polygenic risk score (PRS) analysis. Autosomal genetic variants associated with NAFLD were compared with the MASLD GWAS results. Kaplan-Meier and Cox regression analyses were used to assess associations between MASLD and metabolism-related outcomes.
resultsSixteen single-nucleotide polymorphisms (SNPs) were identified at genome-wide significance levels for MASLD and duplicated in the replication cohort. Differences were found after comparing these SNPs with the results of NAFLD-related genetic variants. MASLD cases with high PRS had a multivariate-adjusted hazard ratio of 3.15 (95% confidence interval, 2.54-3.90) for severe liver disease (SLD), and 2.81 (2.60-3.03) for type 2 diabetes mellitus. The high PRS amplified the impact of MASLD on SLD and extrahepatic outcomes.
conclusionsHigh PRS of MASLD GWAS amplified the impact of MASLD on SLD and metabolism-related outcomes, thereby refining the process of identification of individuals at high risk of MASLD. Supplementation of this process with relevant genetic backgrounds may lead to more effective MASLD prevention and management.
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