| Title: | Polygenic risk score of metabolic dysfunction-associated steatotic liver disease amplifies the health impact on severe liver disease and metabolism-related outcomes |
| Journal: | Journal of Translational Medicine |
| Published: | 12 Jul 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38997780/ |
| DOI: | https://doi.org/10.1186/s12967-024-05478-z |
| URL: | http://dx.doi.org/10.1186/s12967-024-05478-z |
Publication 12844
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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.</p>
17 Keywords
- Aged
- Cohort Studies
- Fatty Liver
- Female
- Genetic Predisposition to Disease
- Genetic Risk Score
- Genome-Wide Association Study
- Humans
- Kaplan-Meier Estimate
- Male
- Metabolic Diseases
- Middle Aged
- Multifactorial Inheritance
- Non-alcoholic Fatty Liver Disease
- Polymorphism, Single Nucleotide
- Proportional Hazards Models
- Risk Factors
14 Authors
- Lushan Xiao
- Yan Li
- Chang Hong
- Pengcheng Ma
- Hongbo Zhu
- Hao Cui
- Xuejing Zou
- Jiaren Wang
- Ruining Li
- Jingzhe He
- Shengxing Liang
- Zeyang Li
- Lin Zeng
- Li Liu
1 Application
| Application ID | Title |
|---|---|
| 92668 | Development and validation of enhanced prediction models based on polygenic analysis and clinical factors for chronic diseases |
Enabling scientific discoveries that improve human health