Research Questions
Are otolaryngological-head & neck disorders-such as hearing loss, chronic rhinosinusitis, and obstructive sleep apnoea-independently associated with the incidence, progression, or mortality risk of diseases across nine systemic domains (cardiovascular, respiratory, neurological, psychiatric, metabolic, renal, skeletal, haematological, and oncological)?
Do multi-omic, imaging, behavioural, and environmental multimodal factors modify or mediate these associations?
Objectives
1.Construct a multi-system chronic-disease atlas (ICD-10 events, cognitive decline, disability, and mortality across the nine domains) and quantify longitudinal hazard ratios for otolaryngological exposures.
2.Integrate molecular (genome, transcriptome, proteome, metabolome, microbiome), imaging (brain MRI, sinus CT, carotid ultrasound), physiological signals (audiograms, sleep studies), clinical & drug data, behavioural & environmental variables, plus text & speech metrics to dissect causal pathways and estimate mediated proportions.
3.Build and validate an interpretable multimodal prediction model that incorporates PRS as a core predictor, estimate 5- and 10-year risks in genetically high-risk (high-PRS), high-pollution, and older sub-groups, and simulate the benefits of intervention.
4.Emulate target randomised controlled trials (Target Trial Emulation, TTE) to estimate causal hazard ratios (HR) and 5-year absolute risk reduction (ARR) of intervention versus non-intervention on the nine systemic outcomes.
Scientific Rationale
Local ENT pathologies can exert systemic effects via inflammation, hypoxia, neural reflexes and the microbe-immune axis. UKB’s deep, multimodal follow-up offers the first population-scale opportunity to quantify these remote impacts and guide precision prevention.
