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The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm

Abstract

Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)1,2,3,4 and type 2 diabetes (T2D)5,6,7, respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 × 10−12) and intracranial aneurysm (OR = 1.29, P = 2.5 × 10−6), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.

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Acknowledgements

We thank the participants whose contribution made this study possible, Noatun (deCODE's sample recruitment center) and the personnel at deCODE core facilities. The recruitment of AAA sample sets and controls from Belgium, Canada and Pennsylvania was funded in part by grants from the US National Heart, Lung and Blood Institute (HL064310 to H.K. and HL044682 to R.E.F.). G.M.L. is a recipient of American Heart Association Predoctoral Fellowships (0510063Z and 0710099Z). The UK AAA sample collection was funded partially from grants from the Medical Research Council and British Heart Foundation. DNA isolation of Dutch AAA samples was funded from a grant from the Novartis Foundation for Cardiovascular Excellence. The Finnish intracranial aneurysm sample collection was funded in part by a US National Institutes of Health grant (NS034395 to G.T.), the American Heart Association, Michigan Affiliate (to G.T.), the University of Kuopio (to A.R.), the University of Helsinki (to J.E.J.) and an American Heart Association Predoctoral Fellowship (0410051Z to S.W.). Y.M. Ruigrok was supported by a grant from the Dr. E. Dekker program of the Netherlands Heart Foundation (2005T014).

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Correspondence to Unnur Thorsteinsdottir or Kari Stefansson.

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Authors from deCODE have stock options in deCODE Genetics. deCODE Genetics has applied for a patent related to this work.

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Helgadottir, A., Thorleifsson, G., Magnusson, K. et al. The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nat Genet 40, 217–224 (2008). https://doi.org/10.1038/ng.72

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