This study aims to utilize the extensive Tier 3 data available through the UK Biobank Research Analysis Platform (UKB-RAP) to advance our understanding of genetic cardiomyopathies. By leveraging the comprehensive genetic, proteomic, and clinical data, we seek to unravel genotype-phenotype relationships and identify novel biomarkers for AOC therapies.
Our primary focus for this proposal will be on RBM20-associated DCM, a particularly aggressive form of the disease. RBM20 is a critical regulator of cardiac-specific alternative splicing, and mutations in its RSRSP region led to severe DCM with an increased risk of sudden cardiac death. By analyzing UK Biobank data, we aim to:
1. Identify and characterize genetic variants in RBM20 across the UK population.
2. Investigate the prevalence and clinical impact of these variants on cardiac function, disease progression, and outcomes.
3. Explore potential genotype-phenotype correlations, focusing on how specific mutations affect disease severity and prognosis.
4. Identify novel biomarkers associated with disease progression and treatment response in RBM20 patients.
5. Develop a risk stratification model for RBM20-DCM based on genetic and clinical data.
This proposal aligns with the UK Biobank’s mission to improve the prevention, diagnosis, and treatment of serious illnesses. With potential expansion to a wide range of genetic cardiomyopathy targets, we will create a robust precision cardiology pipeline that can benefit other cardiovascular diseases in the future.