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

Solveig Gretarsdottir; Annette F Baas; Gudmar Thorleifsson; Hilma Holm; Martin den Heijer; Jean-Paul P M de Vries; Steef E Kranendonk; Clark J A M Zeebregts; Steven M van Sterkenburg; Robert H Geelkerken; Andre M van Rij; Michael J A Williams; Albert P M Boll; Jelena P Kostic; Adalbjorg Jonasdottir; Aslaug Jonasdottir; G Bragi Walters; Gisli Masson; Patrick Sulem; Jona Saemundsdottir; Magali Mouy; Kristinn P Magnusson; Gerard Tromp; James R Elmore; Natzi Sakalihasan; Raymond Limet; Jean-Olivier Defraigne; Robert E Ferrell; Antti Ronkainen; Ynte M Ruigrok; Cisca Wijmenga; Diederick E Grobbee; Svati H Shah; Christopher B Granger; Arshed A Quyyumi; Viola Vaccarino; Riyaz S Patel; A Maziar Zafari; Allan I Levey; Harland Austin; Domenico Girelli; Pier Franco Pignatti; Oliviero Olivieri; Nicola Martinelli; Giovanni Malerba; Elisabetta Trabetti; Lewis C Becker; Diane M Becker; Muredach P Reilly; Daniel J Rader; Thomas Mueller; Benjamin Dieplinger; Meinhard Haltmayer; Sigitas Urbonavicius; Bengt Lindblad; Anders Gottsäter; Eleonora Gaetani; Roberto Pola; Philip Wells; Marc Rodger; Melissa Forgie; Nicole Langlois; Javier Corral; Vicente Vasquez; Jordi Fontcuberta; Francisco España; Niels Grarup; Torben Jørgensen; Daniel R Witte; Torben Hansen; Oluf Pedersen; Katja K Aben; Jacqueline de Graaf; Suzanne Holewijn; Lasse Folkersen; Anders Franco-Cereceda; Per Eriksson; David A Collier; Hreinn Stefansson; Valgerdur Steinthorsdottir; Thorunn Rafnar; Einar M Valdimarsson; Hulda B Magnadottir; Sigurlaug Sveinbjornsdottir; Isleifur Olafsson; Magnus Karl Magnusson; Robert Palmason; Vilhelmina Haraldsdottir; Karl Andersen; Pall T Onundarson; Gudmundur Thorgeirsson; Lambertus A Kiemeney; Janet T Powell; David J Carey; Helena Kuivaniemi; Jes S. Lindholt; Gregory T Jones; Augustine Kong; Jan D Blankensteijn; Stefan E Matthiasson; Unnur Thorsteinsdottir; Kari Stefansson

doi:10.1038/ng.622

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

Solveig Gretarsdottir, Annette F Baas, Gudmar Thorleifsson, Hilma Holm, Martin den Heijer, Jean-Paul P M de Vries, Steef E Kranendonk, Clark J A M Zeebregts, Steven M van Sterkenburg, Robert H Geelkerken, Andre M van Rij, Michael J A Williams, Albert P M Boll, Jelena P Kostic, Adalbjorg Jonasdottir, Aslaug Jonasdottir, G Bragi Walters, Gisli Masson, Patrick Sulem, Jona SaemundsdottirMagali Mouy, Kristinn P Magnusson, Gerard Tromp, James R Elmore, Natzi Sakalihasan, Raymond Limet, Jean-Olivier Defraigne, Robert E Ferrell, Antti Ronkainen, Ynte M Ruigrok, Cisca Wijmenga, Diederick E Grobbee, Svati H Shah, Christopher B Granger, Arshed A Quyyumi, Viola Vaccarino, Riyaz S Patel, A Maziar Zafari, Allan I Levey, Harland Austin, Domenico Girelli, Pier Franco Pignatti, Oliviero Olivieri, Nicola Martinelli, Giovanni Malerba, Elisabetta Trabetti, Lewis C Becker, Diane M Becker, Muredach P Reilly, Daniel J Rader, Thomas Mueller, Benjamin Dieplinger, Meinhard Haltmayer, Sigitas Urbonavicius, Bengt Lindblad, Anders Gottsäter, Eleonora Gaetani, Roberto Pola, Philip Wells, Marc Rodger, Melissa Forgie, Nicole Langlois, Javier Corral, Vicente Vasquez, Jordi Fontcuberta, Francisco España, Niels Grarup, Torben Jørgensen, Daniel R Witte, Torben Hansen, Oluf Pedersen, Katja K Aben, Jacqueline de Graaf, Suzanne Holewijn, Lasse Folkersen, Anders Franco-Cereceda, Per Eriksson, David A Collier, Hreinn Stefansson, Valgerdur Steinthorsdottir, Thorunn Rafnar, Einar M Valdimarsson, Hulda B Magnadottir, Sigurlaug Sveinbjornsdottir, Isleifur Olafsson, Magnus Karl Magnusson, Robert Palmason, Vilhelmina Haraldsdottir, Karl Andersen, Pall T Onundarson, Gudmundur Thorgeirsson, Lambertus A Kiemeney, Janet T Powell, David J Carey, Helena Kuivaniemi, Jes S. Lindholt, Gregory T Jones, Augustine Kong, Jan D Blankensteijn, Stefan E Matthiasson, Unnur Thorsteinsdottir, Kari Stefansson

140 Citationer (Scopus)

Abstract

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 × 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 × 10^-5), peripheral arterial disease (OR = 1.14, P = 3.9 × 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 diseasesĝ€"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.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	42
Udgave nummer	8
Sider (fra-til)	692-7
Antal sider	6
ISSN	1061-4036
DOI	https://doi.org/10.1038/ng.622
Status	Udgivet - 1 aug. 2010

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Gretarsdottir, S., Baas, A. F., Thorleifsson, G., Holm, H., den Heijer, M., de Vries, J-P. P. M., Kranendonk, S. E., Zeebregts, C. J. A. M., van Sterkenburg, S. M., Geelkerken, R. H., van Rij, A. M., Williams, M. J. A., Boll, A. P. M., Kostic, J. P., Jonasdottir, A., Jonasdottir, A., Walters, G. B., Masson, G., Sulem, P., ... Stefansson, K. (2010). Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm. Nature Genetics, 42(8), 692-7. https://doi.org/10.1038/ng.622

Gretarsdottir, S, Baas, AF, Thorleifsson, G, Holm, H, den Heijer, M, de Vries, J-PPM, Kranendonk, SE, Zeebregts, CJAM, van Sterkenburg, SM, Geelkerken, RH, van Rij, AM, Williams, MJA, Boll, APM, Kostic, JP, Jonasdottir, A, Jonasdottir, A, Walters, GB, Masson, G, Sulem, P, Saemundsdottir, J, Mouy, M, Magnusson, KP, Tromp, G, Elmore, JR, Sakalihasan, N, Limet, R, Defraigne, J-O, Ferrell, RE, Ronkainen, A, Ruigrok, YM, Wijmenga, C, Grobbee, DE, Shah, SH, Granger, CB, Quyyumi, AA, Vaccarino, V, Patel, RS, Zafari, AM, Levey, AI, Austin, H, Girelli, D, Pignatti, PF, Olivieri, O, Martinelli, N, Malerba, G, Trabetti, E, Becker, LC, Becker, DM, Reilly, MP, Rader, DJ, Mueller, T, Dieplinger, B, Haltmayer, M, Urbonavicius, S, Lindblad, B, Gottsäter, A, Gaetani, E, Pola, R, Wells, P, Rodger, M, Forgie, M, Langlois, N, Corral, J, Vasquez, V, Fontcuberta, J, España, F, Grarup, N, Jørgensen, T, Witte, DR, Hansen, T , Pedersen, O, Aben, KK, de Graaf, J, Holewijn, S, Folkersen, L, Franco-Cereceda, A, Eriksson, P, Collier, DA, Stefansson, H, Steinthorsdottir, V, Rafnar, T, Valdimarsson, EM, Magnadottir, HB, Sveinbjornsdottir, S, Olafsson, I, Magnusson, MK, Palmason, R, Haraldsdottir, V, Andersen, K, Onundarson, PT, Thorgeirsson, G, Kiemeney, LA, Powell, JT, Carey, DJ, Kuivaniemi, H, Lindholt, JS, Jones, GT, Kong, A, Blankensteijn, JD, Matthiasson, SE, Thorsteinsdottir, U & Stefansson, K 2010, 'Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm', Nature Genetics, bind 42, nr. 8, s. 692-7. https://doi.org/10.1038/ng.622

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

abstract = "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 × 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 × 10-5), peripheral arterial disease (OR = 1.14, P = 3.9 × 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 diseasesĝ€{"}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.",

keywords = "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",

author = "Solveig Gretarsdottir and Baas, {Annette F} and Gudmar Thorleifsson and Hilma Holm and {den Heijer}, Martin and {de Vries}, {Jean-Paul P M} and Kranendonk, {Steef E} and Zeebregts, {Clark J A M} and {van Sterkenburg}, {Steven M} and Geelkerken, {Robert H} and {van Rij}, {Andre M} and Williams, {Michael J A} and Boll, {Albert P M} and Kostic, {Jelena P} and Adalbjorg Jonasdottir and Aslaug Jonasdottir and Walters, {G Bragi} and Gisli Masson and Patrick Sulem and Jona Saemundsdottir and Magali Mouy and Magnusson, {Kristinn P} and Gerard Tromp and Elmore, {James R} and Natzi Sakalihasan and Raymond Limet and Jean-Olivier Defraigne and Ferrell, {Robert E} and Antti Ronkainen and Ruigrok, {Ynte M} and Cisca Wijmenga and Grobbee, {Diederick E} and Shah, {Svati H} and Granger, {Christopher B} and Quyyumi, {Arshed A} and Viola Vaccarino and Patel, {Riyaz S} and Zafari, {A Maziar} and Levey, {Allan I} and Harland Austin and Domenico Girelli and Pignatti, {Pier Franco} and Oliviero Olivieri and Nicola Martinelli and Giovanni Malerba and Elisabetta Trabetti and Becker, {Lewis C} and Becker, {Diane M} and Reilly, {Muredach P} and Rader, {Daniel J} and Thomas Mueller and Benjamin Dieplinger and Meinhard Haltmayer and Sigitas Urbonavicius and Bengt Lindblad and Anders Gotts{\"a}ter and Eleonora Gaetani and Roberto Pola and Philip Wells and Marc Rodger and Melissa Forgie and Nicole Langlois and Javier Corral and Vicente Vasquez and Jordi Fontcuberta and Francisco Espa{\~n}a and Niels Grarup and Torben J{\o}rgensen and Witte, {Daniel R} and Torben Hansen and Oluf Pedersen and Aben, {Katja K} and {de Graaf}, Jacqueline and Suzanne Holewijn and Lasse Folkersen and Anders Franco-Cereceda and Per Eriksson and Collier, {David A} and Hreinn Stefansson and Valgerdur Steinthorsdottir and Thorunn Rafnar and Valdimarsson, {Einar M} and Magnadottir, {Hulda B} and Sigurlaug Sveinbjornsdottir and Isleifur Olafsson and Magnusson, {Magnus Karl} and Robert Palmason and Vilhelmina Haraldsdottir and Karl Andersen and Onundarson, {Pall T} and Gudmundur Thorgeirsson and Kiemeney, {Lambertus A} and Powell, {Janet T} and Carey, {David J} and Helena Kuivaniemi and Lindholt, {Jes S.} and Jones, {Gregory T} and Augustine Kong and Blankensteijn, {Jan D} and Matthiasson, {Stefan E} and Unnur Thorsteinsdottir and Kari Stefansson",

year = "2010",

month = aug,

day = "1",

doi = "10.1038/ng.622",

language = "English",

volume = "42",

pages = "692--7",

journal = "Nature: New biology",

issn = "1061-4036",

publisher = "nature publishing group",

number = "8",

}

TY - JOUR

T1 - Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm

AU - Gretarsdottir, Solveig

AU - Baas, Annette F

AU - Thorleifsson, Gudmar

AU - Holm, Hilma

AU - den Heijer, Martin

AU - de Vries, Jean-Paul P M

AU - Kranendonk, Steef E

AU - Zeebregts, Clark J A M

AU - van Sterkenburg, Steven M

AU - Geelkerken, Robert H

AU - van Rij, Andre M

AU - Williams, Michael J A

AU - Boll, Albert P M

AU - Kostic, Jelena P

AU - Jonasdottir, Adalbjorg

AU - Jonasdottir, Aslaug

AU - Walters, G Bragi

AU - Masson, Gisli

AU - Sulem, Patrick

AU - Saemundsdottir, Jona

AU - Mouy, Magali

AU - Magnusson, Kristinn P

AU - Tromp, Gerard

AU - Elmore, James R

AU - Sakalihasan, Natzi

AU - Limet, Raymond

AU - Defraigne, Jean-Olivier

AU - Ferrell, Robert E

AU - Ronkainen, Antti

AU - Ruigrok, Ynte M

AU - Wijmenga, Cisca

AU - Grobbee, Diederick E

AU - Shah, Svati H

AU - Granger, Christopher B

AU - Quyyumi, Arshed A

AU - Vaccarino, Viola

AU - Patel, Riyaz S

AU - Zafari, A Maziar

AU - Levey, Allan I

AU - Austin, Harland

AU - Girelli, Domenico

AU - Pignatti, Pier Franco

AU - Olivieri, Oliviero

AU - Martinelli, Nicola

AU - Malerba, Giovanni

AU - Trabetti, Elisabetta

AU - Becker, Lewis C

AU - Becker, Diane M

AU - Reilly, Muredach P

AU - Rader, Daniel J

AU - Mueller, Thomas

AU - Dieplinger, Benjamin

AU - Haltmayer, Meinhard

AU - Urbonavicius, Sigitas

AU - Lindblad, Bengt

AU - Gottsäter, Anders

AU - Gaetani, Eleonora

AU - Pola, Roberto

AU - Wells, Philip

AU - Rodger, Marc

AU - Forgie, Melissa

AU - Langlois, Nicole

AU - Corral, Javier

AU - Vasquez, Vicente

AU - Fontcuberta, Jordi

AU - España, Francisco

AU - Grarup, Niels

AU - Jørgensen, Torben

AU - Witte, Daniel R

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Aben, Katja K

AU - de Graaf, Jacqueline

AU - Holewijn, Suzanne

AU - Folkersen, Lasse

AU - Franco-Cereceda, Anders

AU - Eriksson, Per

AU - Collier, David A

AU - Stefansson, Hreinn

AU - Steinthorsdottir, Valgerdur

AU - Rafnar, Thorunn

AU - Valdimarsson, Einar M

AU - Magnadottir, Hulda B

AU - Sveinbjornsdottir, Sigurlaug

AU - Olafsson, Isleifur

AU - Magnusson, Magnus Karl

AU - Palmason, Robert

AU - Haraldsdottir, Vilhelmina

AU - Andersen, Karl

AU - Onundarson, Pall T

AU - Thorgeirsson, Gudmundur

AU - Kiemeney, Lambertus A

AU - Powell, Janet T

AU - Carey, David J

AU - Kuivaniemi, Helena

AU - Lindholt, Jes S.

AU - Jones, Gregory T

AU - Kong, Augustine

AU - Blankensteijn, Jan D

AU - Matthiasson, Stefan E

AU - Thorsteinsdottir, Unnur

AU - Stefansson, Kari

PY - 2010/8/1

Y1 - 2010/8/1

N2 - 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 × 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 × 10-5), peripheral arterial disease (OR = 1.14, P = 3.9 × 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 diseasesĝ€"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.

AB - 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 × 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 × 10-5), peripheral arterial disease (OR = 1.14, P = 3.9 × 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 diseasesĝ€"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.

KW - Alleles

KW - Aortic Aneurysm, Abdominal

KW - Base Sequence

KW - Disease Susceptibility

KW - Genome-Wide Association Study

KW - Humans

KW - Hypertension

KW - Iceland

KW - Myocardial Infarction

KW - Netherlands

KW - Odds Ratio

KW - Risk Factors

KW - ras GTPase-Activating Proteins

U2 - 10.1038/ng.622

DO - 10.1038/ng.622

M3 - Journal article

C2 - 20622881

SN - 1061-4036

VL - 42

SP - 692

EP - 697

JO - Nature: New biology

JF - Nature: New biology

IS - 8

ER -

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

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