Meta-analyses find no genetic link between diabetes and the development of coronary artery disease

August 19, 2020

1 minute read


Disclosures: Van Zuydam reports that she is an employee of AstraZeneca. Please see the study for relevant financial information from all other authors.

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Type 2 diabetes has an established causal association with coronary artery disease, but researchers found no apparent genetic link between diabetes and risk of coronary artery disease, according to a published study. Circulation: genomics and precision medicine.

The investigators performed two meta-analyses that systematically assessed any genetic overlap between coronary artery disease and diabetes in 66,643 people (27,708 with coronary artery disease; 24,259 with diabetes). The first analysis compared CAD cases with controls without reference to diabetes status and the second repeated the analysis and adjusted for diabetes.

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“This study shows that the difference in risk of coronary artery disease between subjects with and without type 2 diabetes cannot be explained by large-effect variants or differences in genetic variation contributing to known risk factors for type 2 diabetes. or coronary artery disease”, Nathalie R. van Zuydam, PhD, researcher in the department of immunology, genetics and pathology at Uppsala University, Sweden, and his colleagues wrote.

Many previously reported loci associated with CAD have been confirmed by researchers to have genome-wide significance (P 5×10-8), which included SORT1/CELSR2, WDR12, PHACTR1, TCF21, 9p21.3CXCL12 and ADAMTS7. This list was expanded to 13 loci in a conjoint analysis.

For established variants of these CAD-associated loci, the risk allele identified in this meta-analysis was the same as the published risk allele for CAD-associated variants (P 1×10-3), which reflects an overlap in the samples included in the analyses, according to the study.

In the second meta-analysis, the researchers reported that three CAD loci achieved genome-wide significance, ADAMTS7 in diabetic patients and 9p21.3 and PHACTR1 in non-diabetic patients, but these did not show a systematic difference according to diabetic status.

The researchers found no new CAD risk signals in either stratum, and the three loci associated with CAD in diabetic patients overlapped with the loci associated with CAD in non-diabetic patients.

“There are several other mechanisms, outside the scope of the current study, that may explain some of the increased risk of coronary artery disease in subjects with type 2 diabetes,” van Zuydam and colleagues wrote. “There could be epigenetic changes induced by certain features of the type 2 diabetes condition. For example, hyperglycemia has been shown to cause epigenetic changes altering gene expression in vascular cells leading to a endothelial dysfunction, a hallmark of atherosclerosis.

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