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Published in: Diabetologia 10/2018

Open Access 01-10-2018 | Short Communication

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

Authors: Tove Fall, Stefan Gustafsson, Marju Orho-Melander, Erik Ingelsson

Published in: Diabetologia | Issue 10/2018

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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.
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Literature
1.
go back to reference Emerging Risk Factors C, Sarwar N, Gao P et al (2010) Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375:2215–2222CrossRef Emerging Risk Factors C, Sarwar N, Gao P et al (2010) Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375:2215–2222CrossRef
2.
go back to reference Eastwood SV, Mathur R, Atkinson M et al (2016) Algorithms for the Capture and Adjudication of Prevalent and Incident Diabetes in UK Biobank. PLoS One 11:e0162388CrossRefPubMedPubMedCentral Eastwood SV, Mathur R, Atkinson M et al (2016) Algorithms for the Capture and Adjudication of Prevalent and Incident Diabetes in UK Biobank. PLoS One 11:e0162388CrossRefPubMedPubMedCentral
4.
go back to reference Chang CC, Chow CC, Tellier LC, Vattikuti S, Purcell SM, Lee JJ (2015) Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4:7CrossRefPubMedPubMedCentral Chang CC, Chow CC, Tellier LC, Vattikuti S, Purcell SM, Lee JJ (2015) Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4:7CrossRefPubMedPubMedCentral
6.
7.
8.
go back to reference Nikpay M, Goel A, Won HH et al (2015) A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet 47:1121–1130CrossRefPubMedPubMedCentral Nikpay M, Goel A, Won HH et al (2015) A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet 47:1121–1130CrossRefPubMedPubMedCentral
9.
go back to reference Qi L, Qi Q, Prudente S et al (2013) Association between a genetic variant related to glutamic acid metabolism and coronary heart disease in individuals with type 2 diabetes. JAMA 310:821–828CrossRefPubMed Qi L, Qi Q, Prudente S et al (2013) Association between a genetic variant related to glutamic acid metabolism and coronary heart disease in individuals with type 2 diabetes. JAMA 310:821–828CrossRefPubMed
10.
go back to reference Doney AS, Fischer B, Leese G, Morris AD, Palmer CN (2004) Cardiovascular risk in type 2 diabetes is associated with variation at the PPARG locus: a Go-DARTS study. Arterioscler Thromb Vasc Biol 24:2403–2407CrossRefPubMed Doney AS, Fischer B, Leese G, Morris AD, Palmer CN (2004) Cardiovascular risk in type 2 diabetes is associated with variation at the PPARG locus: a Go-DARTS study. Arterioscler Thromb Vasc Biol 24:2403–2407CrossRefPubMed
11.
go back to reference Musunuru K, Strong A, Frank-Kamenetsky M et al (2010) From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature 466:714–719CrossRefPubMedPubMedCentral Musunuru K, Strong A, Frank-Kamenetsky M et al (2010) From noncoding variant to phenotype via SORT1 at the 1p13 cholesterol locus. Nature 466:714–719CrossRefPubMedPubMedCentral
12.
go back to reference Liu X, El-Mahdy MA, Boslett J et al (2017) Cytoglobin regulates blood pressure and vascular tone through nitric oxide metabolism in the vascular wall. Nat Commun 8:14807CrossRefPubMedPubMedCentral Liu X, El-Mahdy MA, Boslett J et al (2017) Cytoglobin regulates blood pressure and vascular tone through nitric oxide metabolism in the vascular wall. Nat Commun 8:14807CrossRefPubMedPubMedCentral
13.
go back to reference Howson JMM, Zhao W, Barnes DR et al (2017) Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms. Nat Genet 49:1113–1119CrossRefPubMedPubMedCentral Howson JMM, Zhao W, Barnes DR et al (2017) Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms. Nat Genet 49:1113–1119CrossRefPubMedPubMedCentral
Metadata
Title
Genome-wide association study of coronary artery disease among individuals with diabetes: the UK Biobank
Authors
Tove Fall
Stefan Gustafsson
Marju Orho-Melander
Erik Ingelsson
Publication date
01-10-2018
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 10/2018
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-018-4686-z

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