This project aims to leverage UK Biobank’s comprehensive multi-modal dataset to improve our understanding of genetic and non-genetic risk factors contributing to diseases of impaired muscle function, particularly focusing on cardiovascular disorders (heart failure, hypertrophic cardiomyopathy) and neuromuscular conditions through integrated analysis of genomics, proteomic biomarkers, and electronic health record data.
Our key research objectives:
– Identify novel genetic variants and proteomic biomarkers associated with both cardiac and skeletal muscle function by analyzing whole genome sequencing data, proteomic profiles, and multi-modal imaging phenotypes (cardiac imaging and derived phenotypes) from the UK Biobank cohort.
– Investigate the relationship between muscle metabolism markers and disease outcomes in both cardiovascular and neuromuscular conditions using metabolomic and proteomic data, combined with detailed imaging measurements.
– Develop predictive models for patient stratification across muscle-related diseases by integrating genomic sequencing data, biochemical assay measurements and repeated imaging assessment using machine learning approaches.
– Study the impact of clonal hematopoiesis of indeterminate potential (CHIP) on cardiovascular outcomes and treatment response in medical conditions with impaired muscle function.
Scientific rationale:
UK Biobank’s unprecedented scale of multi-modal data provides a unique opportunity to study causal human biology and molecular pathophysiology underlying diseases of impaired muscle function. By combining genetic insights with proteomic biomarker discovery, we aim to identify novel therapeutic targets and develop more precise approaches for patient stratification across both cardiovascular and neuromuscular conditions. This research will support our ongoing development of muscle-directed therapies including cardiac myosin modulators and advance our understanding of muscle biology in health and disease.
