Unraveling ‘F’ factor: towards a genetic-clinical framework for the musculoskeletal-heart crosstalk in metabolic aging
Authors' conclusion
Our findings provide converging evidence for Musculoskeletal-Heart crosstalk of metabolic aging and inferred the 'F' factor as a genetic correlate of a transdiagnostic state, which links genetic predisposition to metabolic dysregulation, and systemic functional decline. This work provides a multi-level biological characterization of multimorbidity liability, informing early-risk detection and preventive strategies for complex aging-related comorbidities.
Study context
- Population
- China Health and Retirement Longitudinal Study (CHARLS) cohort; GWAS data for coronary artery disease, T2D, hypertension, BMD, frailty and telomere length
- Outcome
- CMM risk prediction with Frailty-Integrated Indices; shared latent genetic 'F' factor
Methodological detailsmachine learning with SHAP interpretation, Genomic-SEM, fine-mapping, transcriptome-wide association study (TWAS), gene-based analysis, functional annotation
- Machine learning with SHAP interpretation
- Genomic-SEM
- Fine-mapping
- TWAS
- Gene-based analysis
- Functional annotation
Main finding
As reported in the abstract
Several Frailty-Integrated Indices significantly improved cardiometabolic multimorbidity (CMM) risk prediction; optimal model AUC
0.727
Observational data: associations, not effects.
Original publication
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