Causal association and genetic correlation of frailty with metabolic dysfunction-associated steatotic liver disease: Epidemiological and genetic analyses
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PUBLIC SUMMARY
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The risk of metabolic dysfunction-associated fatty liver disease (MASLD) increases significantly with frailty.
There was a significant causal and positive genetic correlation between frailty and MASLD.
Early clinical frailty screening can identify high-risk populations for MASLD before liver damage occurs.
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ABSTRACT
Frailty has become a major public health issue, but its association with Metabolic dysfunction-associated steatotic liver disease (MASLD) remains controversial. We conducted an observational study of frailty and MASLD using the frailty index (FI) and frailty phenotype (FP) in the UK Biobank. And the results were validated in the National Health and the All of Us Research Program (AoU) database. We explored the causal relationship and genetic correlation between frailty and MASLD. In the UK population, both pre-frail and frail individuals had increased risks of MASLD in the analyses of FI and FP. Notably, the odds ratios of FI to the occurrence of MASLD were even more significant in our study in the US population. The odds ratios were 2.75 ([95% CI 2.41-3.15]; P<0.001) for pre-frailty and 6.88 (95% CI 6.02-7.90; P<0.001) for frailty. There was significant causality (OR 2.00; [95% CI 1.40-2.86]; P<0.001) and positive genetic correlations (LDSC: rg =0.576, P<0.001; GNOVA: rg =0.777, P<0.001; ρ-HESS: rg =0.828) between FP and MASLD. Frailty greatly increases the risk of developing MASLD. There was a significant causal and positive genetic correlation between FP and MASLD. -
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REFERENCES
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Zhang H., Li L., Zhang L., et al. (2025). Causal association and genetic correlation of frailty with metabolic dysfunction-associated steatotic liver disease: Epidemiological and genetic analyses. The Innovation Medicine 3:100155. https://doi.org/10.59717/j.xinn-med.2025.100155
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Zhang H., Li L., Zhang L., et al. (2025). Causal association and genetic correlation of frailty with metabolic dysfunction-associated steatotic liver disease: Epidemiological and genetic analyses. The Innovation Medicine 3:100155. https://doi.org/10.59717/j.xinn-med.2025.100155
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Figure 1.
Forest plot of subgroup interaction effects on pre-frailty (frailty index)
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Figure 2.
Forest plot of subgroup interaction effects on frailty (frailty index)
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Figure 3.
Forest plot of subgroup interaction effects on pre-frailty (frailty phenotype)
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Figure 4.
Forest plot of subgroup interaction effects on frailty (frailty phenotype)
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Figure 5.
The results of genetic analysis of frailty and MASLD
