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

Anna Helgadottir; Gudmar Thorleifsson; Kristinn P. Magnusson; Solveig Grétarsdottir; Valgerdur Steinthorsdottir; Andrei Manolescu; Gregory T. Jones; Gabriel J.E. Rinkel; Jan D. Blankensteijn; Antti Ronkainen; Juha E. Jääskeläinen; Yoshiki Kyo; Guy M. Lenk; Natzi Sakalihasan; Konstantinos Kostulas; Anders Gottsäter; Andrea Flex; Hreinn Stefansson; Torben Hansen; Gitte Andersen; Shantel Weinsheimer; Knut Borch-Johnsen; Torben Jorgensen; Svati H. Shah; Arshed A. Quyyumi; Christopher B. Granger; Muredach P. Reilly; Harland Austin; Allan I. Levey; Viola Vaccarino; Ebba Palsdottir; G. Bragi Walters; Thorbjorg Jonsdottir; Steinunn Snorradottir; Dana Magnusdottir; Gudmundur Gudmundsson; Robert E. Ferrell; Sigurlaug Sveinbjornsdottir; Juha Hernesniemi; Mika Niemelä; Raymond Limet; Karl Andersen; Gunnar Sigurdsson; Rafn Benediktsson; Eric L.G. Verhoeven; Joep A.W. Teijink; Diederick E. Grobbee; Daniel J. Rader; David A. Collier; Oluf Pedersen; Roberto Pola; Jan Hillert; Bengt Lindblad; Einar M. Valdimarsson; Hulda B. Magnadottir; Cisca Wijmenga; Gerard Tromp; Annette F. Baas; Ynte M. Ruigrok; Andre M. Van Rij; Helena Kuivaniemi; Janet T. Powell; Stefan E. Matthiasson; Jeffrey R. Gulcher; Gudmundur Thorgeirsson; Augustine Kong; Unnur Thorsteinsdottir; Kari Stefansson

doi:10.1038/ng.72

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

Anna Helgadottir, Gudmar Thorleifsson, Kristinn P. Magnusson, Solveig Grétarsdottir, Valgerdur Steinthorsdottir, Andrei Manolescu, Gregory T. Jones, Gabriel J.E. Rinkel, Jan D. Blankensteijn, Antti Ronkainen, Juha E. Jääskeläinen, Yoshiki Kyo, Guy M. Lenk, Natzi Sakalihasan, Konstantinos Kostulas, Anders Gottsäter, Andrea Flex, Hreinn Stefansson, Torben Hansen, Gitte AndersenShantel Weinsheimer, Knut Borch-Johnsen, Torben Jorgensen, Svati H. Shah, Arshed A. Quyyumi, Christopher B. Granger, Muredach P. Reilly, Harland Austin, Allan I. Levey, Viola Vaccarino, Ebba Palsdottir, G. Bragi Walters, Thorbjorg Jonsdottir, Steinunn Snorradottir, Dana Magnusdottir, Gudmundur Gudmundsson, Robert E. Ferrell, Sigurlaug Sveinbjornsdottir, Juha Hernesniemi, Mika Niemelä, Raymond Limet, Karl Andersen, Gunnar Sigurdsson, Rafn Benediktsson, Eric L.G. Verhoeven, Joep A.W. Teijink, Diederick E. Grobbee, Daniel J. Rader, David A. Collier, Oluf Pedersen, Roberto Pola, Jan Hillert, Bengt Lindblad, Einar M. Valdimarsson, Hulda B. Magnadottir, Cisca Wijmenga, Gerard Tromp, Annette F. Baas, Ynte M. Ruigrok, Andre M. Van Rij, Helena Kuivaniemi, Janet T. Powell, Stefan E. Matthiasson, Jeffrey R. Gulcher, Gudmundur Thorgeirsson, Augustine Kong, Unnur Thorsteinsdottir^*, Kari Stefansson

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

563 Citations (Scopus)

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) 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.

Original language	English
Pages (from-to)	217-224
Number of pages	8
Journal	Nature Genetics
Volume	40
Issue number	2
DOIs	https://doi.org/10.1038/ng.72
Publication status	Published - Feb 2008

Bibliographical note

Funding Information:
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).

Access to Document

10.1038/ng.72

Cite this

Helgadottir, A., Thorleifsson, G., Magnusson, K. P., Grétarsdottir, S., Steinthorsdottir, V., Manolescu, A., Jones, G. T., Rinkel, G. J. E., Blankensteijn, J. D., Ronkainen, A., Jääskeläinen, J. E., Kyo, Y., Lenk, G. M., Sakalihasan, N., Kostulas, K., Gottsäter, A., Flex, A., Stefansson, H., Hansen, T., ... Stefansson, K. (2008). The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nature Genetics, 40(2), 217-224. https://doi.org/10.1038/ng.72

@article{116c690b6ee74c7181eae208c3634b5d,

title = "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) 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.",

author = "Anna Helgadottir and Gudmar Thorleifsson and Magnusson, {Kristinn P.} and Solveig Gr{\'e}tarsdottir and Valgerdur Steinthorsdottir and Andrei Manolescu and Jones, {Gregory T.} and Rinkel, {Gabriel J.E.} and Blankensteijn, {Jan D.} and Antti Ronkainen and J{\"a}{\"a}skel{\"a}inen, {Juha E.} and Yoshiki Kyo and Lenk, {Guy M.} and Natzi Sakalihasan and Konstantinos Kostulas and Anders Gotts{\"a}ter and Andrea Flex and Hreinn Stefansson and Torben Hansen and Gitte Andersen and Shantel Weinsheimer and Knut Borch-Johnsen and Torben Jorgensen and Shah, {Svati H.} and Quyyumi, {Arshed A.} and Granger, {Christopher B.} and Reilly, {Muredach P.} and Harland Austin and Levey, {Allan I.} and Viola Vaccarino and Ebba Palsdottir and Walters, {G. Bragi} and Thorbjorg Jonsdottir and Steinunn Snorradottir and Dana Magnusdottir and Gudmundur Gudmundsson and Ferrell, {Robert E.} and Sigurlaug Sveinbjornsdottir and Juha Hernesniemi and Mika Niemel{\"a} and Raymond Limet and Karl Andersen and Gunnar Sigurdsson and Rafn Benediktsson and Verhoeven, {Eric L.G.} and Teijink, {Joep A.W.} and Grobbee, {Diederick E.} and Rader, {Daniel J.} and Collier, {David A.} and Oluf Pedersen and Roberto Pola and Jan Hillert and Bengt Lindblad and Valdimarsson, {Einar M.} and Magnadottir, {Hulda B.} and Cisca Wijmenga and Gerard Tromp and Baas, {Annette F.} and Ruigrok, {Ynte M.} and {Van Rij}, {Andre M.} and Helena Kuivaniemi and Powell, {Janet T.} and Matthiasson, {Stefan E.} and Gulcher, {Jeffrey R.} and Gudmundur Thorgeirsson and Augustine Kong and Unnur Thorsteinsdottir and Kari Stefansson",

note = "Funding Information: We thank the participants whose contribution made this study possible, Noatun (deCODE{\textquoteright}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).",

year = "2008",

month = feb,

doi = "10.1038/ng.72",

language = "English",

volume = "40",

pages = "217--224",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "2",

}

Helgadottir, A, Thorleifsson, G, Magnusson, KP, Grétarsdottir, S, Steinthorsdottir, V, Manolescu, A, Jones, GT, Rinkel, GJE, Blankensteijn, JD, Ronkainen, A, Jääskeläinen, JE, Kyo, Y, Lenk, GM, Sakalihasan, N, Kostulas, K, Gottsäter, A, Flex, A, Stefansson, H, Hansen, T, Andersen, G, Weinsheimer, S, Borch-Johnsen, K, Jorgensen, T, Shah, SH, Quyyumi, AA, Granger, CB, Reilly, MP, Austin, H, Levey, AI, Vaccarino, V, Palsdottir, E, Walters, GB, Jonsdottir, T, Snorradottir, S, Magnusdottir, D, Gudmundsson, G, Ferrell, RE, Sveinbjornsdottir, S, Hernesniemi, J, Niemelä, M, Limet, R, Andersen, K, Sigurdsson, G, Benediktsson, R, Verhoeven, ELG, Teijink, JAW, Grobbee, DE, Rader, DJ, Collier, DA, Pedersen, O, Pola, R, Hillert, J, Lindblad, B, Valdimarsson, EM, Magnadottir, HB, Wijmenga, C, Tromp, G, Baas, AF, Ruigrok, YM, Van Rij, AM, Kuivaniemi, H, Powell, JT, Matthiasson, SE, Gulcher, JR, Thorgeirsson, G, Kong, A, Thorsteinsdottir, U & Stefansson, K 2008, 'The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm', Nature Genetics, vol. 40, no. 2, pp. 217-224. https://doi.org/10.1038/ng.72

TY - JOUR

T1 - The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm

AU - Helgadottir, Anna

AU - Thorleifsson, Gudmar

AU - Magnusson, Kristinn P.

AU - Grétarsdottir, Solveig

AU - Steinthorsdottir, Valgerdur

AU - Manolescu, Andrei

AU - Jones, Gregory T.

AU - Rinkel, Gabriel J.E.

AU - Blankensteijn, Jan D.

AU - Ronkainen, Antti

AU - Jääskeläinen, Juha E.

AU - Kyo, Yoshiki

AU - Lenk, Guy M.

AU - Sakalihasan, Natzi

AU - Kostulas, Konstantinos

AU - Gottsäter, Anders

AU - Flex, Andrea

AU - Stefansson, Hreinn

AU - Hansen, Torben

AU - Andersen, Gitte

AU - Weinsheimer, Shantel

AU - Borch-Johnsen, Knut

AU - Jorgensen, Torben

AU - Shah, Svati H.

AU - Quyyumi, Arshed A.

AU - Granger, Christopher B.

AU - Reilly, Muredach P.

AU - Austin, Harland

AU - Levey, Allan I.

AU - Vaccarino, Viola

AU - Palsdottir, Ebba

AU - Walters, G. Bragi

AU - Jonsdottir, Thorbjorg

AU - Snorradottir, Steinunn

AU - Magnusdottir, Dana

AU - Gudmundsson, Gudmundur

AU - Ferrell, Robert E.

AU - Sveinbjornsdottir, Sigurlaug

AU - Hernesniemi, Juha

AU - Niemelä, Mika

AU - Limet, Raymond

AU - Andersen, Karl

AU - Sigurdsson, Gunnar

AU - Benediktsson, Rafn

AU - Verhoeven, Eric L.G.

AU - Teijink, Joep A.W.

AU - Grobbee, Diederick E.

AU - Rader, Daniel J.

AU - Collier, David A.

AU - Pedersen, Oluf

AU - Pola, Roberto

AU - Hillert, Jan

AU - Lindblad, Bengt

AU - Valdimarsson, Einar M.

AU - Magnadottir, Hulda B.

AU - Wijmenga, Cisca

AU - Tromp, Gerard

AU - Baas, Annette F.

AU - Ruigrok, Ynte M.

AU - Van Rij, Andre M.

AU - Kuivaniemi, Helena

AU - Powell, Janet T.

AU - Matthiasson, Stefan E.

AU - Gulcher, Jeffrey R.

AU - Thorgeirsson, Gudmundur

AU - Kong, Augustine

AU - Thorsteinsdottir, Unnur

AU - Stefansson, Kari

N1 - Funding Information: 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).

PY - 2008/2

Y1 - 2008/2

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=38649091662&partnerID=8YFLogxK

U2 - 10.1038/ng.72

DO - 10.1038/ng.72

M3 - Article

C2 - 18176561

AN - SCOPUS:38649091662

SN - 1061-4036

VL - 40

SP - 217

EP - 224

JO - Nature Genetics

JF - Nature Genetics

IS - 2

ER -

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

Abstract

Bibliographical note

Access to Document

Fingerprint

Cite this