Genome-wide association study of coronary artery disease among individuals with diabetes: the UK Biobank

Abstract

Aims/hypothesis: 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. Methods: 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. Results: 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. Conclusions/interpretation: 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.