Inflammatory Bowel Disease (IBD) and Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD/MASLD) are major global health burdens. Epidemiological overlap suggests shared or interacting risk factors. This project will systematically identify and compare modifiable and non-modifiable risk factors for each disease independently within the UK Biobank (UKB), then investigate their interplay in co-occurrence.
Research Questions:
Which key lifestyle (e.g., diet, activity, smoking, alcohol), metabolic (e.g., obesity, diabetes), medication use, and environmental factors are independently associated with IBD risk in UKB?
Which key lifestyle, metabolic, medication use, and environmental factors are independently associated with MAFLD/MASLD risk in UKB?
How do the identified risk factor profiles differ between IBD and MAFLD/MASLD? What are the distinct vs. overlapping risk factor sets?
Which specific factors or combinations are most strongly associated with IBD and MAFLD/MASLD co-occurrence?
Objectives:
Identify significant risk factors for incident/prevalent IBD using multivariable regression (adjusting for confounders).
Identify significant risk factors for MAFLD/MASLD using analogous methods.
Directly compare strength/direction/significance of risk factors from Obj. 1 & 2 to delineate disease-specific vs. shared profiles.
Use interaction/mediation analyses to determine how risk factors for one disease influence the other and drive co-occurrence.
Scientific Rationale: Defining robust population-level risk profiles for IBD and MAFLD/MASLD separately is fundamental for prevention. UKB’s unparalleled size (~500,000), deep phenotyping (imaging, biomarkers, questionnaires), longitudinal follow-up (linked health records), and genetic data enable these large-scale, comparative analyses with power to control for complex confounders. Findings will inform targeted prevention for both individual diseases and their co-occurrence.