Coronary artery disease (CAD) is a common complication among individuals with diabetes. A better understanding of the genetic background of CAD in this population has the potential to suggest novel molecular targets for screening, risk assessment and drug development.
We performed a genome-wide association study of CAD in 15,666 unrelated individuals (3,968 CAD cases and 11,698 controls) of white British ancestry with diabetes at inclusion in the UK Biobank study. Our results were compared with results from participants without diabetes.
We found genome-wide significant evidence for association with CAD at the previously well-established LPA locus (lead variant: rs74617384; OR 1.38 [95% CI 1.26, 1.51], p = 3.2 10-12) and at 9p21 (lead variant: rs10811652; OR 1.19 [95% CI 1.13, 1.26], p = 6.0 10-11). Moreover, other variants previously associated with CAD showed similar effects in the participants with and without diabetes, indicating that the genetic architecture of CAD is largely the same.
Our results indicate large similarities between the genetic architecture of CAD in participants with and without diabetes. Larger studies are needed to establish whether there are important diabetes-specific CAD loci.
Causal associations of circulating biomarkers with cardiovascular disease
The overall goal of this project is to study the causal roles of the 36 biomarkers currently being assayed in UK Biobank for development of coronary heart disease, stroke and heart failure. Knowledge about causal relations of these 36 biomarkers with cardiovascular outcomes will give important insights regarding the etiological understanding of these diseases and accelerate development of new prevention strategies, including druggable targets. Hence, the proposed research does meet UK Biobank's stated purpose via improving the prevention and treatment of heart disease and stroke.
First, we will study associations of 36 circulating biomarkers representing different biological systems with incidence of coronary heart disease, stroke and heart failure.
Second, by combing data from the UK Biobank gene analyses with the biomarker data, we will perform genetic studies across the whole human genome for all 36 biomarkers to establish common genetic variation associated with respective biomarker.
Third, we will perform so called Mendelian randomization analyses to study whether the biomarkers are causally related to coronary heart disease, stroke and heart failure.
Full cohort (n=502,650).
|Lead investigator:||Prof. Themistocles Assimes|
|Lead institution:||Stanford University|