Cardiovascular Disease (CVD) is a leading cause of death and produces immense health and economic burdens worldwide. While advances have been made in understanding the complex pathogenic processes on a range of major clinical heart and circulatory disease conditions, translation of genetic findings for improved diagnosis or prevention of CVD has not materialized in a meaningful way. There is a critical need to identify causal pathways and biological mechanisms involved in the development of CVD through integrative systems genetics strategies and identify the gene-environment (GxE) interactions using the large size of UK Biobank data, which could lead to the development of potentially novel therapeutic strategies in highly susceptible individuals. The genotype and clinical binary and quantitative traits we request from all UK Biobank participants will be used for statistical analyses. Based on the combined statistical expertise of our team, we are confident that the proposed studies can all be accomplished with the scope of 3 years. By investigating the genetic basis of major cardiovascular conditions and cardiometabolic risk factor traits, our proposed analyses will shed additional light on the causal pathway and biological mechanisms underlying the development of CVD and identify novel therapeutic targets and/or risk stratification tools. Therefore, these studies would be consistent with UK Biobank’s stated purpose to improve the prevention, diagnosis and treatment of a wide range of illnesses, including heart diseases.
