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

• Published in: Nature Genetics
• Main Authors: Gretarsdottir, Solveig, Baas, Annette F, Thorleifsson, Gudmar, Holm, Hilma, den Heijer, Martin, de Vries, Jean-Paul P M, Kranendonk, Steef E, Zeebregts, Clark J A M, van Sterkenburg, Steven M, Geelkerken, Robert H, van Rij, Andre M, Williams, Michael J A, Boll, Albert P M, Kostic, Jelena P, Jonasdottir, Adalbjorg, Jonasdottir, Aslaug, Walters, G Bragi, Masson, Gisli, Sulem, Patrick, Saemundsdottir, Jona, Mouy, Magali, Magnusson, Kristinn P, Tromp, Gerard, Elmore, James R, Sakalihasan, Natzi, Limet, Raymond, Defraigne, Jean-Olivier, Ferrell, Robert E, Ronkainen, Antti, Ruigrok, Ynte M, Wijmenga, Cisca, Grobbee, Diederick E, Shah, Svati H, Granger, Christopher B, Quyyumi, Arshed A, Vaccarino, Viola, Patel, Riyaz S, Zafari, A Maziar, Levey, Allan I, Austin, Harland, Girelli, Domenico, Pignatti, Pier Franco, Olivieri, Oliviero, Martinelli, Nicola, Malerba, Giovanni, Trabetti, Elisabetta, Becker, Lewis C, Becker, Diane M, Reilly, Muredach P, Rader, Daniel J, Mueller, Thomas, Dieplinger, Benjamin, Haltmayer, Meinhard, Urbonavicius, Sigitas, Lindblad, Bengt, Gottsäter, Anders, Gaetani, Eleonora, Pola, Roberto, Wells, Philip, Rodger, Marc, Forgie, Melissa, Langlois, Nicole, Corral, Javier, Vasquez, Vicente, Fontcuberta, Jordi, España, Francisco, Grarup, Niels, Jørgensen, Torben, Witte, Daniel R, Hansen, Torben, Pedersen, Oluf, Aben, Katja K, de Graaf, Jacqueline, Holewijn, Suzanne, Folkersen, Lasse, Franco-Cereceda, Anders, Eriksson, Per, Collier, David A, Stefansson, Hreinn, Steinthorsdottir, Valgerdur, Rafnar, Thorunn, Valdimarsson, Einar M, Magnadottir, Hulda B, Sveinbjornsdottir, Sigurlaug, Olafsson, Isleifur, Magnusson, Magnus Karl, Palmason, Robert, Haraldsdottir, Vilhelmina, Andersen, Karl, Onundarson, Pall T, Thorgeirsson, Gudmundur, Kiemeney, Lambertus A, Powell, Janet T, Carey, David J, Kuivaniemi, Helena, Lindholt, Jes S, Jones, Gregory T, Kong, Augustine, Blankensteijn, Jan D, Matthiasson, Stefan E, Thorsteinsdottir, Unnur, Stefansson, Kari
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2010
• Subjects: Alleles; Aortic Aneurysm; Abdominal; Base Sequence; Disease Susceptibility; Genome-Wide Association Study; Humans; Hypertension; Iceland; Myocardial Infarction; Netherlands; Odds Ratio; Risk Factors; ras GTPase-Activating Proteins
• Online Access: https://portal.findresearcher.sdu.dk/da/publications/ff53bbde-d8dd-430c-83f2-8cdc37585126; https://doi.org/10.1038/ng.622

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 x 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 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 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 diseases-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.