Letter abstract
Nature Genetics 40, 217 - 224 (2008)
Published online: 6 January 2008 | doi:10.1038/ng.72
The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm
Anna Helgadottir1,29, Gudmar Thorleifsson1,29, Kristinn P Magnusson1,29, Solveig Grétarsdottir1, Valgerdur Steinthorsdottir1, Andrei Manolescu1, Gregory T Jones2, Gabriel J E Rinkel3, Jan D Blankensteijn4, Antti Ronkainen5, Juha E Jääskeläinen5, Yoshiki Kyo6, Guy M Lenk6, Natzi Sakalihasan7, Konstantinos Kostulas8, Anders Gottsäter9, Andrea Flex10, Hreinn Stefansson1, Torben Hansen11, Gitte Andersen11, Shantel Weinsheimer6, Knut Borch-Johnsen11,12,13, Torben Jorgensen13, Svati H Shah14, Arshed A Quyyumi15, Christopher B Granger14, Muredach P Reilly16, Harland Austin15, Allan I Levey15, Viola Vaccarino15, Ebba Palsdottir1, G Bragi Walters1, Thorbjorg Jonsdottir1, Steinunn Snorradottir1, Dana Magnusdottir1, Gudmundur Gudmundsson1, Robert E Ferrell17, Sigurlaug Sveinbjornsdottir18, Juha Hernesniemi19, Mika Niemelä19, Raymond Limet7, Karl Andersen18, Gunnar Sigurdsson18,20, Rafn Benediktsson18,20, Eric L G Verhoeven21, Joep A W Teijink22, Diederick E Grobbee23, Daniel J Rader16, David A Collier24, Oluf Pedersen11,12, Roberto Pola10, Jan Hillert8, Bengt Lindblad9, Einar M Valdimarsson18, Hulda B Magnadottir18, Cisca Wijmenga25,26, Gerard Tromp6, Annette F Baas23, Ynte M Ruigrok3, Andre M van Rij2, Helena Kuivaniemi6, Janet T Powell27, Stefan E Matthiasson28, Jeffrey R Gulcher1, Gudmundur Thorgeirsson18,28, Augustine Kong1, Unnur Thorsteinsdottir1,28 & Kari Stefansson1,28
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.
- deCODE Genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.
- Vascular Research Group, Otago Medical School, PO Box 913, Dunedin 9054, New Zealand.
- Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
- Department of Vascular Surgery, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
- Department of Neurosurgery, Kuopio University Hospital, Kuopio, Finland.
- Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
- University Hospital of Liège, Department of Cardiovascular Surgery, B-4000 Liège, Belgium.
- Department of Neurology, Karolinska Institutet at Karolinska University Hospital, S-141 86 Huddinge, Sweden.
- University of Lund, Department of Vascular Diseases, Malmö University Hospital, S-205 02 Malmö, Sweden.
- Department of Medicine, A. Gemelli University Hospital, L.go A. Gemelli 8, 00168 Rome, Italy.
- Steno Diabetes Center, DK-2820 Copenhagen, Denmark.
- Faculty of Health Science, University of Aarhus, DK-8000 Aarhus, Denmark.
- Research Centre for Prevention and Health, Glostrup University Hospital, DK-2600 Glostrup, Denmark.
- Duke University School of Medicine, Durham, North Carolina 27710, USA.
- Emory University School of Medicine, Atlanta, Georgia 30322, USA.
- University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
- Department of Human Genetics, University of Pittsburgh, School of Public Health, Pittsburgh, Pennsylvania 15261, USA
- Landspitali University Hospital, IS-101 Reykjavik, Iceland.
- Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, P.O. Box 266 FI-00029 HUS, Finland.
- Icelandic Heart Association, 201 Kopavogur, Iceland.
- Department of Surgery, University Medical Center Groningen, University of Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.
- Department of Surgery, Atrium Medical Center, Heerlen, P.O. Box 4446,6401 CX, The Netherlands.
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.
- Division of Psychological Medicine and Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Box 63, De Crespigny Park, London SE5 8AF, UK.
- Department of Genetics, University Medical Centre (UMCG), 9700 Groningen, The Netherlands.
- Complex Genetics Section, Department of Biomedical Genetics, University Medical Centre Utrecht, 3508 AB Utrecht, The Netherlands.
- Vascular Surgery Research Group, Imperial College at Charing Cross, St Dunstan's Rd, London W6 8RP, UK.
- University of Iceland, School of Medicine, 101 Reykjavik, Iceland.
- These authors contributed equally to this work.
Correspondence to: Kari Stefansson1,28 e-mail: kstefans@decode.is
Correspondence to: Unnur Thorsteinsdottir1,28 e-mail: unnur.thorsteinsdottir@decode.is
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