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

• Published in: Nature genetics Vol. 40; no. 2; pp. 217 - 224
• Main Authors: Borch-Johnsen, Knut, van Rij, Andre M, Baas, Annette F, Blankensteijn, Jan D, Snorradottir, Steinunn, Sigurdsson, Gunnar, Niemelä, Mika, Weinsheimer, Shantel, Hernesniemi, Juha, Stefansson, Hreinn, Gudmundsson, Gudmundur, Kostulas, Konstantinos, Jonsdottir, Thorbjorg, Teijink, Joep A W, Benediktsson, Rafn, Jones, Gregory T, Grétarsdottir, Solveig, Walters, G Bragi, Verhoeven, Eric L G, Sakalihasan, Natzi, Magnusson, Kristinn P, Grobbee, Diederick E, Hansen, Torben, Kyo, Yoshiki, Powell, Janet T, Ruigrok, Ynte M, Kuivaniemi, Helena, Tromp, Gerard, Helgadottir, Anna, Thorleifsson, Gudmar, Kong, Augustine, Stefansson, Kari, Gulcher, Jeffrey R, Lenk, Guy M, Magnusdottir, Dana, Rinkel, Gabriel J E, Gottsäter, Anders, Vaccarino, Viola, Hillert, Jan, Ferrell, Robert E, Andersen, Karl, Granger, Christopher B, Levey, Allan I, Jorgensen, Torben, Collier, David A, Magnadottir, Hulda B, Thorsteinsdottir, Unnur, Thorgeirsson, Gudmundur, Lindblad, Bengt, Jääskeläinen, Juha E, Flex, Andrea, Quyyumi, Arshed A, Rader, Daniel J, Pedersen, Oluf, Pola, Roberto, Reilly, Muredach P, Wijmenga, Cisca, Sveinbjornsdottir, Sigurlaug, Limet, Raymond, Shah, Svati H, Austin, Harland, Matthiasson, Stefan E, Andersen, Gitte, Palsdottir, Ebba, Valdimarsson, Einar M, Steinthorsdottir, Valgerdur, Manolescu, Andrei, Ronkainen, Antti
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-02-2008; Nature Publishing Group
• Subjects: Adult; Aged; Agriculture; Alleles; Aneurysms; Animal Genetics and Genomics; Aortic Aneurysm, Abdominal - epidemiology; Aortic Aneurysm, Abdominal - genetics; Aortic Aneurysm, Abdominal - physiopathology; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cardiac and Cardiovascular Systems; Cardiology. Vascular system; Cardiovascular disease; Case-Control Studies; Chi-Square Distribution; Chromosomes, Human, Pair 9; Classical genetics, quantitative genetics, hybrids; Clinical Medicine; Complications and side effects; Coronary heart disease; Diabetes; Diagnosis; European Continental Ancestry Group; Female; Fundamental and applied biological sciences. Psychology; Gene Frequency; Gene Function; Genetic aspects; Genetic Markers; Genetic Variation; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Haplotypes; Heart; Homozygote; Human Genetics; Humans; Intracranial Aneurysm - genetics; Intracranial Aneurysm - physiopathology; Kardiologi; Klinisk medicin; letter; Likelihood Functions; Linkage Disequilibrium; Male; Medical and Health Sciences; Medical sciences; Medicin och hälsovetenskap; Methods, theories and miscellaneous; Middle Aged; Myocardial infarction; Myocardial Infarction - genetics; Myocardial Infarction - physiopathology; Neurology; Odds Ratio; Physiological aspects; Polymorphism, Single Nucleotide; Prevalence; Probability; Risk Factors; Sequence Analysis, DNA; Single nucleotide polymorphisms; Type 2 diabetes; Vascular diseases and vascular malformations of the nervous system; United States; Genetic mapping; Myocardial infarction; Nervous system diseases; Cardiovascular disease; Coronary heart disease; Myocardial disease; Aortic aneurysm; Cerebral disorder; Vascular disease; Variant; intracranial aneurysm; Central nervous system disease; Cerebrovascular disease
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.72

Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), 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.