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Approved research

A Mendelian Randomisation Study to Assess the Interaction between ADCY9 rs1967309, HDL, Diet and Atherosclerosis Measured by Carotid Intima Media Thickness (CIMT).

Principal Investigator: Dr Patrick Gladding
Approved Research ID: 25602
Approval date: May 14th 2018

Lay summary

Raising HDL, using medication, has not been shown to improve cardiovascular outcomes, despite epidemiological studies showing that high HDL is beneficial. A recent genome-wide-association study has shown that the HDL raising drug, dalcetrapib, reduces cardiovascular events and atheroma in patients with a particular genotype. This effect may be either gene-drug or gene-HDL related. We propose a mendelian randomisation study to evaluate the relationship between de novo HDL levels and the ADCY9 rs1967309 and its influence on carotid artery intima media thickness (CIMT), as a marker of atherosclerosis. UK Biobank's stated purpose is to support health-related research that is in the public's interest. Our study will have wide relevance to population health given the high prevalence of atherosclerosis, and morbidity/mortality associated with the disease. If a relationship is shown to exist between HDL and the ADCY9 gene, which is independent of dalcetrapib, then this drug-gene association will be more widely relevant to the population, even in the absence of this drug. Both the drug and the gene test are patented. No biological samples in the UK Biobank will be used in this study. Subjects will be identified by their HDL levels. Subjects who have undergone CIMT testing will be stratified by their HDL levels. Subjects in the lowest and highest HDL quartile will be evaluated to test the relationship between CIMT and the ADCY9 gene. This project can be completed with only electronic data and will not require consumption of biological samples. The CIMT subset of the full cohort will be used. This study will only be possible if either the ADCY9 rs1967309 SNP has been tested on the UK Biobank array or can be imputed from the existing data.