Research Question
Physical-psychological-cognitive multimorbidity (PPCMM)-the co-occurrence of chronic somatic disorders , depression/anxiety, and cognitive impairment/dementia-dramatically increases disability, mortality, and healthcare costs. Global data show that low socioeconomic status raises PPCMM odds >10-fold, yet the molecular pathways that mechanistically link systemic disease, mental health, and cognition remain poorly defined. Leveraging UK Biobank’s longitudinal multi-omics, deep imaging, digital-phenotyping, and geocoded environmental exposures, we propose a comprehensive investigation to:
Objectives
1. Discover residual risk factors beyond traditional metrics: integrate genomics, proteomics, metabolomics, microbiome, imaging and exposomic data.
2. Quantify how lifestyle factors (diet, physical activity, sleep, substance use) and environmental stressors (air pollution, noise, neighbourhood deprivation) modify these biological pathways..
3. Examine the role of emerging risk factors in primary and secondary prevention to guide early prevention and clinical application.
4. Develop integrative risk models combining genetic, proteomic, environmental, and lifestyle data for personalized prevention strategies.
Scientific Rationale
The UK Biobank enables comprehensive investigation of somatic-psychological-cognitive multimorbidity through integrated !longitudinal multi-omics data, deep phenotyping, and quantified environmental exposures.Proteomics reveals systemic biomarkers linking peripheral inflammation to neuroinflammation and cognitive decline. Metabolomics identifies dysregulated pathways connecting somatic disorders to depression. Neuroimaging captures structural/functional brain alterations mediating psychological-cognitive comorbidity. Genomics (PRS) disentangles genetic susceptibility from environmental triggers.
