Approved Research

Independent and combined associations of modifiable risk factors and multi-omics with non-communicable diseases and mortality

Lay summary

Non-communicable diseases (NCDs) are the major causes of death worldwide. The recent advances in high-throughput technology have facilitated the integrative analysis of multi-omics data to identify causal genes and underlying molecular mechanisms that are involved in the progression of cardiometabolic diseases, which will be vital in identifying novel biomarkers, understanding disease etiology, and further facilitating risk stratification. In particular, the development of metabolomics allows for quantifying the individual-level biomolecular response to genetic, lifestyle, environmental, and clinical risk factors, which provides important insights into deciphering the biological pathways between risk factors and cardiometabolic diseases. However, large-scale epidemiological data applying the multi-omics techniques remained scarce.

The UK Biobank has comprehensive data on individual exposures, genetics, proteomics, metabolomics, and follow-up outcomes in a large-scale population, which provides a unique opportunity to evaluate the independent and combined effects of modifiable risk factors and multi-omics on cardiometabolic diseases. In this study, we aim to examine the association of modifiable risk factors with cardiometabolic diseases and related mortality outcomes and explore the underlying mechanisms using multi-omics (transcriptomics, metabolomics, proteomics, and genomics) techniques. Moreover, we will use genetic, proteomic, and metabolomic data to identify phenotypes associated with cardiometabolic diseases, identify high-risk populations, and further examine the association of modifiable risk factors with cardiometabolic diseases among people with different risk stratifications.

The research project is initially planned for 3 years but might be extended if promising first results are obtained. The findings will help to understand the disease etiology of cardiometabolic diseases, identify novel biomarkers for risk prediction and targets for intervention, and examine mechanisms through which these modifiable risk factors affect the health outcomes. Collectively, this project will inform the development of personalized preventive and therapeutic strategies and provide insights into reducing the global burden of cardiometabolic diseases.