While substantial progress has been made in identifying genetic susceptibility loci, multi-domain exposures (encompassing environmental factors, sociodemographic determinants, lifestyle behaviors, and metabolic dysregulation), and population-level environmental drivers for chronic non-communicable diseases (NCDs) and associated mortality, critical gaps persist in understanding their molecular mediation mechanisms. Capitalizing on the UK Biobank’s comprehensive multi-omics dataset integrating genomic profiles, longitudinal metabolomic measurements, and granular exposure assessments, this investigation proposes to:
1. Establish Metabolic Precursors of NCD Pathogenesis
Conduct prospective analyses of baseline plasma metabolomes using multi-dimensional survival models to identify:
Disease-specific metabolic signatures for six major NCD categories (hypertension, T2D, CVD, cancer, respiratory/digestive disorders, neurocognitive decline);
Mortality-associated metabolic trajectories;
2. Delineate Multimorbidity Transition Pathways
Develop system medicine frameworks to model: Temporal metabolic shifts during single-to-multi disease progression; Exposure-mediated acceleration of comorbidity networks; Composite risk signatures integrating longitudinal metabolomic fluxes with multi-omic profiles to inform precision prevention frameworks.
