Research Questions: How do genetic, metabolic, and environmental determinants interact to drive the pathogenesis, progression, and clinical outcomes of complex cardiovascular diseases, with a specific focus on aortic aneurysm, aortic dissection, and atherosclerosis? What are the underlying systemic molecular networks that can serve as novel targets for early diagnosis and therapeutic intervention?
Objectives: 1) To systematically identify novel genetic architectures, including rare variants and gene-environment interactions, associated with the susceptibility and progression of aortic and atherosclerotic diseases.
2) To leverage the extensive genomic, metabolomic, and proteomic datasets within the UK Biobank to construct multi-omics integration models, elucidating systemic metabolic reprogramming and cross-tissue communication mechanisms.
3) To discover and clinically validate novel biomarkers and therapeutic targets, facilitating drug repurposing screening and precision medicine strategies for cardiovascular risk stratification and management.
Scientific Rationale: Aortic diseases and atherosclerosis represent life-threatening conditions with complex, multifactorial etiologies characterized by dynamic vascular remodeling, inflammation, and metabolic dysfunction. The UK Biobank offers an unparalleled, large-scale prospective cohort equipped with deep genomic data paired with comprehensive biochemical, metabolomic, and longitudinal clinical phenotyping. By employing advanced bioinformatics, integrative multi-omics network analyses, and machine learning algorithms, this project aims to decode the multi-dimensional biological mechanisms underlying vascular pathogenesis. Ultimately, translating these comprehensive insights will provide a robust evidence base for identifying critical signaling axes, optimizin