This project aims to elucidate the molecular mechanisms underlying the onset and progression of diabetic retinopathy (DR) by leveraging the UK Biobank’s genomic, plasma proteomic, and metabolomic resources. The key research question is: what molecular pathways and causal biomarkers drive DR development, and how can integrated multi!omics analyses identify early diagnostic and prognostic markers while clarifying genetic-protein interactions that underlie disease progression? By linking genetic variation, circulating proteins, metabolites, and ophthalmic phenotypes, the study will identify causal biomarkers and construct a scalable multi!omics framework to uncover disease pathways. The analytical strategy integrates genome!wide association studies, proteomic and metabolomic profiling, and genetic-protein interaction analyses to detect early molecular perturbations and delineate the transition from diabetes to DR.
DR is a leading cause of vision loss, yet its early molecular drivers remain poorly defined because current diagnostics rely on retinal imaging after irreversible damage has occurred. UK Biobank uniquely combines large!scale genomic, proteomic, metabolomic, and ophthalmic data, providing an unprecedented opportunity to dissect disease etiology at the population level. Multi!omics integration with genetic methods will distinguish upstream molecular drivers from downstream correlates, reveal mediating metabolic pathways, and enable robust causal inference through Mendelian randomization and colocalization.
All analyses will be conducted independently under the UK Biobank Student Tier, with strict adherence to data security and usage policies. The findings will form the core of the doctoral thesis and support peer!reviewed publications with the student as first author, contributing to early risk stratification and precision prevention strategies for diabetic retinopathy.