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 Jørgensen; 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 Jørgensen, 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

560 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 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 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
Journal	Nature Genetics
Volume	40
Issue number	2
Pages (from-to)	217-24
Number of pages	7
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.72
Publication status	Published - 2008

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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), 217-24. https://doi.org/10.1038/ng.72

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, Jørgensen, 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. 217-24. https://doi.org/10.1038/ng.72

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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 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 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 J{\o}rgensen 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 = "Keywords: Adult; Aged; Alleles; Aortic Aneurysm, Abdominal; Case-Control Studies; Chi-Square Distribution; Chromosomes, Human, Pair 9; European Continental Ancestry Group; Female; Gene Frequency; Genetic Markers; Genetic Variation; Haplotypes; Homozygote; Humans; Intracranial Aneurysm; Likelihood Functions; Linkage Disequilibrium; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Polymorphism, Single Nucleotide; Prevalence; Probability; Risk Factors; Sequence Analysis, DNA",

year = "2008",

doi = "10.1038/ng.72",

language = "English",

volume = "40",

pages = "217--24",

journal = "Nature: New biology",

issn = "1061-4036",

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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 - Jørgensen, 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 - Keywords: Adult; Aged; Alleles; Aortic Aneurysm, Abdominal; Case-Control Studies; Chi-Square Distribution; Chromosomes, Human, Pair 9; European Continental Ancestry Group; Female; Gene Frequency; Genetic Markers; Genetic Variation; Haplotypes; Homozygote; Humans; Intracranial Aneurysm; Likelihood Functions; Linkage Disequilibrium; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Polymorphism, Single Nucleotide; Prevalence; Probability; Risk Factors; Sequence Analysis, DNA

PY - 2008

Y1 - 2008

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 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 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 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 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.

U2 - 10.1038/ng.72

DO - 10.1038/ng.72

M3 - Journal article

C2 - 18176561

SN - 1061-4036

VL - 40

SP - 217

EP - 224

JO - Nature: New biology

JF - Nature: New biology

IS - 2

ER -

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

Abstract

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