Linking Genomics to Imaging data: Elucidation of the mechanisms of novel genes that predispose to heart disease

Genome wide studies have provided great insight into the truly polygenic nature of cardiovascular disease, with current meta-analysis being performed in populations of ~200,000 study individuals.  This has characterised around 60 loci involved in susceptibility to CAD.  This analysis combines a wide range of cardiovascular phenotypes including angina, IMT, atheroplasty and MI. So the role of these genes in individual components of cardiovascular disease such as atherosclerosis, vessel damage, heart muscle physiology etc. has not yet been elucidated. In order for us to take this knowledge forward to providing useful stratification we need to understand further the role of genes on individual intermediate phenotypes in cardiovascular disease, and MRI imaging provides a unique window to provide pathological intermediate phenotypes for the understanding of the mechanisms by which the genes are impacting on cardiovascular outcomes.

The goal of the project will be to genotype 60 confirmed CAD variants in a group of individuals where everybody has had a full body MRI image performed.  These will be examined for association with various MRI angiographic phenotypes including Total and regional atherosclerotic Burden, and cardiac structural phenotypes. The SNPs will be examined individually and grouped together into gene scores for greater power and pathway analysis.  This should reveal important information regarding the mechanism by which these genes modulate risk for cardiovascular disease and may provide novel strategies for the prevention of heart disease in the genetically “at risk” population.  This project would suit a highly numerate student who has an aptitude for computing and/or statistics.

Professor Colin Palmer
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