Research aim: Our research focuses on elucidating the combined effects of inherited genetic variation, circulating metabolomic and proteomic profiles, and modifiable exposures-including lifestyle, diet, treatment history, and environmental pollutants-on the risk and progression of major skin diseases (eczema, psoriasis, melanoma) using UK Biobank data. Current clinical risk models rely mainly on family history or single biomarkers, overlooking the complex, multi-layered biological mechanisms involved. UK Biobank’s rich resource includes genome-wide genotypes, targeted metabolomics (~200 metabolites), SomaScan proteomics (~5,000 proteins), and detailed lifestyle/environmental data, enabling integrative analysis.
Scientific rationale:Previous studies implicate accelerated biological aging, systemic inflammation, and disturbed metabolic pathways in skin barrier dysfunction, but causal links remain unclear. By combining polygenic risk scores, multi-omics data, and quantified environmental exposures through multivariable modeling and Mendelian randomization, we aim to dissect disease mechanisms and identify actionable biomarkers and modifiable risk factors.
Methods & timeline:The project is structured in four overlapping phases over 36 months: data curation and quality control (months 1-6), univariate and PRS analyses (6-18), multi-omics integration and modeling (12-30), and causal inference with validation (24-36).
Expected impact: Our study anticipates revealing integrated molecular and environmental risk profiles that enable personalized risk stratification and early intervention for individuals predisposed to severe skin diseases. Identifying modifiable exposures and biomarkers can guide targeted prevention strategies, such as lifestyle or dietary modifications, and inform development of novel therapeutics, ultimately improving public health by reducing disease burden.
