Mental and physical health problems frequently co-occur, creating heavy burdens and complex care needs. Prior work implicates lifestyle, multilevel environmental and social exposures, and polygenic liability, but the precise bio-psycho-social mechanisms and interactions that drive progression from single conditions to comorbidity/multimorbidity remain unclear. Using UK Biobank’s deeply phenotyped cohort with linked health records, biomarkers, and multimodal brain imaging, this project will: (1) identify environmental, biological, psychological, and social risk and resilience factors for mental and physical health outcomes and their comorbidities; (2) investigate pathways linking health problems, lifestyle/behaviour, psychological factors (e.g., symptoms, stress, loneliness), biomarkers, neuroimaging features, and multilevel environmental and social exposures; and (3) test lifestyle × environment/social × biomarker (e.g., genetics) interactions and explore the interplay of bio-psycho-social factors. Clinically, we aim to build an evidence base for risk stratification and early screening that integrates bio-psycho-social information to enable earlier, individualised interventions. From a public-health perspective, we will quantify the impact of modifiable factors and place-based disparities to inform health-system planning and targeted population interventions, prioritising high-risk communities (e.g., trauma-exposed populations, populations with neurodevelopmental diagnoses) to reduce the burden of comorbidity and multimorbidity. The project is designed for completion within three years.
