Primary Questions:
1. What are the modifiable and non-modifiable risk factors (lifestyle, environmental, clinical) associated with incident cardiometabolic diseases (e.g., T2DM, hypertension) and ischemic diseases (e.g., CAD, stroke) in the UK population?
2. How do genetic variants (common and rare) interact with environmental factors to influence disease risk?
3. Can we identify novel biomarkers or polygenic risk scores (PRS) to stratify high-risk populations?
Aims:
1. To perform comprehensive phenome-wide association studies (PheWAS) for cardiometabolic and ischemic traits.
2. To integrate genomic data (SNPs, CNVs) with metabolomic/proteomic data for mechanistic insights.
3. To develop predictive models combining genetic and clinical variables.
A3. Background and Scientific Rationale
Cardiometabolic and ischemic diseases account for 30% of global mortality, yet their multifactorial etiology remains incompletely understood. While UK Biobank has enabled genome-wide studies (e.g., GWAS), gaps persist in:
– Multi-omics integration: Limited studies combine genomics with serum biomarkers (e.g., NMR metabolomics) and imaging (e.g., cardiac MRI).
– Sex/ethnic disparities: Underrepresentation in risk prediction models.
– Gene-environment interactions: e.g., how diet modifies genetic risk.
This project will leverage UK Biobank’s scale (~500,000 participants) to address these gaps, aligning with the UK’s NHS Long Term Plan to prioritize cardiovascular prevention.
