Respiratory diseases commonly coexist with cardiometabolic, neuropsychological, immune-mediated and musculoskeletal conditions, giving rise to complex patterns of multimorbidity. Despite increasing recognition of these clustered disease trajectories, the extent to which inherited genetic susceptibility interacts with environmental exposures, such as air pollution, green space, aeroallergens (e.g., pollen), to influence the onset, progression and systemic complications of respiratory multimorbidity remains insufficiently characterized. Existing studies often examine single respiratory endpoints and rarely extend findings to downstream multimorbidity trajectories. Population-based evidence jointly integrating genomics, exposome profiles, lifestyle, biomarkers and longitudinal multimorbidity progression remains scarce. The UK Biobank, with its large-scale genomic resources, comprehensive environmental exposure metrics and long-term clinical follow-up, provides an unparalleled opportunity to address these gaps.
To systematically address these gaps and advance understanding of how genetic, environmental and early-life factors shape respiratory multimorbidity, this project has four aims:
1. Identify multimorbidity patterns involving major respiratory diseases and their systemic comorbidities across the life course.
2. Quantify the independent and joint effects of genetic predisposition (GWAS, polygenic risk scores, functional variants) and environmental exposures (air pollution, built environment, climate, allergens, occupational agents, early-life antibiotic exposure) on disease onset and progression.
3. Examine gene-environment interactions in the development and worsening of respiratory multimorbidity.
4. Develop risk-prediction models integrating genomics, exposome profiles and biomarkers for early identification of high-risk individuals.