Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm

Solveig Gretarsdottir, Annette F. Baas, Gudmar Thorleifsson, Hilma Holm, Martin Den Heijer, Jean Paul P.M. De Vries, Steef E. Kranendonk, Clark J.A.M. Zeebregts, Steven M. Van Sterkenburg, Robert H. Geelkerken, Andre M. Van Rij, Michael J.A. Williams, Albert P.M. Boll, Jelena P. Kostic, Adalbjorg Jonasdottir, Aslaug Jonasdottir, G. Bragi Walters, Gisli Masson, Patrick Sulem, Jona SaemundsdottirMagali Mouy, Kristinn P. Magnusson, Gerard Tromp, James R. Elmore, Natzi Sakalihasan, Raymond Limet, Jean Olivier Defraigne, Robert E. Ferrell, Antti Ronkainen, Ynte M. Ruigrok, Cisca Wijmenga, Diederick E. Grobbee, Svati H. Shah, Christopher B. Granger, Arshed A. Quyyumi, Viola Vaccarino, Riyaz S. Patel, A. Maziar Zafari, Allan I. Levey, Harland Austin, Domenico Girelli, Pier Franco Pignatti, Oliviero Olivieri, Nicola Martinelli, Giovanni Malerba, Elisabetta Trabetti, Lewis C. Becker, Diane M. Becker, Muredach P. Reilly, Daniel J. Rader, Thomas Mueller, Benjamin Dieplinger, Meinhard Haltmayer, Sigitas Urbonavicius, Bengt Lindblad, Anders Gottsäter, Eleonora Gaetani, Roberto Pola, Philip Wells, Marc Rodger, Melissa Forgie, Nicole Langlois, Javier Corral, Vicente Vicente, Jordi Fontcuberta, Francisco España, Niels Grarup, Torben Jørgensen, Daniel R. Witte, Torben Hansen, Oluf Pedersen, Katja K. Aben, Jacqueline De Graaf, Suzanne Holewijn, Lasse Folkersen, Anders Franco-Cereceda, Per Eriksson, David A. Collier, Hreinn Stefansson, Valgerdur Steinthorsdottir, Thorunn Rafnar, Einar M. Valdimarsson, Hulda B. Magnadottir, Sigurlaug Sveinbjornsdottir, Isleifur Olafsson, Magnus Karl Magnusson, Robert Palmason, Vilhelmina Haraldsdottir, Karl Andersen, Pall T. Onundarson, Gudmundur Thorgeirsson, Lambertus A. Kiemeney, Janet T. Powell, David J. Carey, Helena Kuivaniemi, Jes S. Lindholt, Gregory T. Jones, Augustine Kong, Jan D. Blankensteijn, Stefan E. Matthiasson, Unnur Thorsteinsdottir, Kari Stefansson

Research output: Contribution to journalArticle

Abstract

We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 × 10 -10. In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 × 10-5), peripheral arterial disease (OR = 1.14, P = 3.9 × 10-5) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseasesĝ€"that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.

Original languageEnglish (US)
Pages (from-to)692-697
Number of pages6
JournalNature genetics
Volume42
Issue number8
DOIs
StatePublished - Aug 1 2010

ASJC Scopus subject areas

  • Genetics

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    Gretarsdottir, S., Baas, A. F., Thorleifsson, G., Holm, H., Den Heijer, M., De Vries, J. P. P. M., Kranendonk, S. E., Zeebregts, C. J. A. M., Van Sterkenburg, S. M., Geelkerken, R. H., Van Rij, A. M., Williams, M. J. A., Boll, A. P. M., Kostic, J. P., Jonasdottir, A., Jonasdottir, A., Walters, G. B., Masson, G., Sulem, P., ... Stefansson, K. (2010). Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm. Nature genetics, 42(8), 692-697. https://doi.org/10.1038/ng.622