Genome-wide association study of intracranial aneurysm identifies three new risk loci

Katsuhito Yasuno; Kaya Bilguvar; Philippe Bijlenga; Siew Kee Low; Boris Krischek; Georg Auburger; Matthias Simon; Dietmar Krex; Zulfikar Arlier; Nikhil Nayak; Ynte M. Ruigrok; Mika Niemelä; Atsushi Tajima; Mikael Von Und Zu Fraunberg; Tamás Dóczi; Florentina Wirjatijasa; Akira Hata; Jordi Blasco; Agi Oszvald; Hidetoshi Kasuya; Gulam Zilani; Beate Schoch; Pankaj Singh; Carsten Stüer; Roelof Risselada; Jürgen Beck; Teresa Sola; Filomena Ricciardi; Arpo Aromaa; Thomas Illig; Stefan Schreiber; Cornelia M. Van Duijn; Leonard H. Van Den Berg; Claire Perret; Carole Proust; Constantin Roder; Ali K. Ozturk; Emília Gaál; Daniela Berg; Christof Geisen; Christoph M. Friedrich; Paul Summers; Alejandro F. Frangi; Matthew W. State; H. Erich Wichmann; Monique M.B. Breteler; Cisca Wijmenga; Shrikant Mane; Leena Peltonen; Vivas Elio; Miriam C.J.M. Sturkenboom; Patricia Lawford; James Byrne; Juan MacHo; Erol I. Sandalcioglu; Bernhard Meyer; Andreas Raabe; Helmuth Steinmetz; Daniel Rüfenacht; Juha E. Jääskeläinen; Juha Hernesniemi; Gabriel J.E. Rinkel; Hitoshi Zembutsu; Ituro Inoue; Aarno Palotie; François Cambien; Yusuke Nakamura; Richard P. Lifton; Murat Günel

doi:10.1038/ng.563

Genome-wide association study of intracranial aneurysm identifies three new risk loci

Katsuhito Yasuno
, Kaya Bilguvar
, Philippe Bijlenga
, Siew Kee Low
, Boris Krischek
, Georg Auburger
, Matthias Simon
, Dietmar Krex
, Zulfikar Arlier
, Nikhil Nayak
, Ynte M. Ruigrok
, Mika Niemelä
, Atsushi Tajima
, Mikael Von Und Zu Fraunberg
, Tamás Dóczi
, Florentina Wirjatijasa
, Akira Hata
, Jordi Blasco
, Agi Oszvald
, Hidetoshi Kasuya

Gulam Zilani, Beate Schoch, Pankaj Singh, Carsten Stüer, Roelof Risselada, Jürgen Beck, Teresa Sola, Filomena Ricciardi, Arpo Aromaa, Thomas Illig, Stefan Schreiber, Cornelia M. Van Duijn, Leonard H. Van Den Berg, Claire Perret, Carole Proust, Constantin Roder, Ali K. Ozturk, Emília Gaál, Daniela Berg, Christof Geisen, Christoph M. Friedrich, Paul Summers, Alejandro F. Frangi, Matthew W. State, H. Erich Wichmann, Monique M.B. Breteler, Cisca Wijmenga, Shrikant Mane, Leena Peltonen, Vivas Elio, Miriam C.J.M. Sturkenboom, Patricia Lawford, James Byrne, Juan MacHo, Erol I. Sandalcioglu, Bernhard Meyer, Andreas Raabe, Helmuth Steinmetz, Daniel Rüfenacht, Juha E. Jääskeläinen, Juha Hernesniemi, Gabriel J.E. Rinkel, Hitoshi Zembutsu, Ituro Inoue, Aarno Palotie, François Cambien, Yusuke Nakamura, Richard P. Lifton, Murat Günel

Technical University of Munich

Yale University Medical School
Geneva University Hospitals
University of Tokyo
University of Tübingen
Johann Wolfgang Goethe University
University of Bonn
Universitätsklinikum Carl Gustav Carus Dresden
Rudolf Magnus Institute of Neuroscience
Helsinki University Central Hospital
Tokai University
Kuopion Yliopistollinen sairaala
University of Pecs Medical School
Chiba-U
Hospital Clinic Barcelona
Tokyo Women's University
University of Oxford Medical Sciences Division
University Hospital of Essen
University of Sheffield
Royal Hallamshire Hospital
Technical University of Munich
Erasmus University Medical Center
Hospital General de Catalunya
National Institute for Health and Welfare
Helmholtz Zentrum München German Research Center for Environmental Health
Christian-Albrechts-University of Kiel
Netherlands Consortium for Health Aging
AP-HP
Nephrology German Red Cross (DRK) Hospital Berlin-Köpenick
Fraunhofer-Institut für Algorithmen und Wissenschaftliches Rechnen SCAI
Pompeu Fabra University (UPF)
Biomateriales y Nanomedicina (CIBER-BBN)
Technology Department
Child Study Center, Yale University School of Medicine
University Medical Center Groningen
Yale University
Wellcome Sanger Institute
University of Helsinki
Hirslanden Klinik Aarau

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

258 Scopus citations

Abstract

Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,891 cases and 14,181 controls with 832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 18q11.2 (odds ratio (OR) = 1.22, P = 1.1 × 10 12), STARD13-KL on 13q13.1 (OR = 1.20, P = 2.5 × 10 9) and a gene-rich region on 10q24.32 (OR = 1.29, P = 1.2 × 10 9). We also confirmed prior associations near SOX17 (8q11.23-q12.1; OR = 1.28, P = 1.3 × 10 12) and CDKN2A-CDKN2B (9p21.3; OR = 1.31, P = 1.5 × 10 22). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair.

Original language	English
Pages (from-to)	420-425
Number of pages	6
Journal	Nature Genetics
Volume	42
Issue number	5
DOIs	https://doi.org/10.1038/ng.563
State	Published - May 2010

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Yasuno, K., Bilguvar, K., Bijlenga, P., Low, S. K., Krischek, B., Auburger, G., Simon, M., Krex, D., Arlier, Z., Nayak, N., Ruigrok, Y. M., Niemelä, M., Tajima, A., Von Und Zu Fraunberg, M., Dóczi, T., Wirjatijasa, F., Hata, A., Blasco, J., Oszvald, A., ... Günel, M. (2010). Genome-wide association study of intracranial aneurysm identifies three new risk loci. Nature Genetics, 42(5), 420-425. https://doi.org/10.1038/ng.563

@article{19b60080cf014412893222ea106e91fc,

title = "Genome-wide association study of intracranial aneurysm identifies three new risk loci",

abstract = "Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,891 cases and 14,181 controls with 832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 18q11.2 (odds ratio (OR) = 1.22, P = 1.1 × 10 12), STARD13-KL on 13q13.1 (OR = 1.20, P = 2.5 × 10 9) and a gene-rich region on 10q24.32 (OR = 1.29, P = 1.2 × 10 9). We also confirmed prior associations near SOX17 (8q11.23-q12.1; OR = 1.28, P = 1.3 × 10 12) and CDKN2A-CDKN2B (9p21.3; OR = 1.31, P = 1.5 × 10 22). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair.",

author = "Katsuhito Yasuno and Kaya Bilguvar and Philippe Bijlenga and Low, \{Siew Kee\} and Boris Krischek and Georg Auburger and Matthias Simon and Dietmar Krex and Zulfikar Arlier and Nikhil Nayak and Ruigrok, \{Ynte M.\} and Mika Niemel{\"a} and Atsushi Tajima and \{Von Und Zu Fraunberg\}, Mikael and Tam{\'a}s D{\'o}czi and Florentina Wirjatijasa and Akira Hata and Jordi Blasco and Agi Oszvald and Hidetoshi Kasuya and Gulam Zilani and Beate Schoch and Pankaj Singh and Carsten St{\"u}er and Roelof Risselada and J{\"u}rgen Beck and Teresa Sola and Filomena Ricciardi and Arpo Aromaa and Thomas Illig and Stefan Schreiber and \{Van Duijn\}, \{Cornelia M.\} and \{Van Den Berg\}, \{Leonard H.\} and Claire Perret and Carole Proust and Constantin Roder and Ozturk, \{Ali K.\} and Em{\'i}lia Ga{\'a}l and Daniela Berg and Christof Geisen and Friedrich, \{Christoph M.\} and Paul Summers and Frangi, \{Alejandro F.\} and State, \{Matthew W.\} and Wichmann, \{H. Erich\} and Breteler, \{Monique M.B.\} and Cisca Wijmenga and Shrikant Mane and Leena Peltonen and Vivas Elio and Sturkenboom, \{Miriam C.J.M.\} and Patricia Lawford and James Byrne and Juan MacHo and Sandalcioglu, \{Erol I.\} and Bernhard Meyer and Andreas Raabe and Helmuth Steinmetz and Daniel R{\"u}fenacht and J{\"a}{\"a}skel{\"a}inen, \{Juha E.\} and Juha Hernesniemi and Rinkel, \{Gabriel J.E.\} and Hitoshi Zembutsu and Ituro Inoue and Aarno Palotie and Fran{\c c}ois Cambien and Yusuke Nakamura and Lifton, \{Richard P.\} and Murat G{\"u}nel",

note = "Funding Information: We are grateful to the participants who made this study possible.We thank A. Chamberlain, B. Meseck-Selchow and members of the Keck Foundation Biotechnology Resource Laboratory for their technical help. This study was supported by the Yale Center for Human Genetics and Genomics and the Yale Program on Neurogenetics, the US National Institutes of Health (NIH) grants R01NS057756 (M.G.) and U24 NS051869 (S.M.) and the Howard Hughes Medical Institute (R.P.L.). This study is partially funded by the European Commission under the 6th Framework Programme through the @neurIST (www.aneurist.org) project under contract no. FP6-IST-2004-027703. The Frankfurt case cohort collection was supported by Bundesministerium f{\"u}r Bildung und Forschung (01GI9907), Utrecht Control cohort by the Prinses Beatrix Fonds and the Adessium foundation (L.H.v.d.B.). S.M. was supported in part by the Clinical and Translational Science Award UL1 RR024139, National Center for Research Resources, NIH.We would also like to acknowledge the use of Yale University Biomedical High Performance Computing Center (NIH grant: RR19895).",

year = "2010",

month = may,

doi = "10.1038/ng.563",

language = "English",

volume = "42",

pages = "420--425",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "5",

}

Yasuno, K, Bilguvar, K, Bijlenga, P, Low, SK, Krischek, B, Auburger, G, Simon, M, Krex, D, Arlier, Z, Nayak, N, Ruigrok, YM, Niemelä, M, Tajima, A, Von Und Zu Fraunberg, M, Dóczi, T, Wirjatijasa, F, Hata, A, Blasco, J, Oszvald, A, Kasuya, H, Zilani, G, Schoch, B, Singh, P, Stüer, C, Risselada, R, Beck, J, Sola, T, Ricciardi, F, Aromaa, A, Illig, T, Schreiber, S, Van Duijn, CM, Van Den Berg, LH, Perret, C, Proust, C, Roder, C, Ozturk, AK, Gaál, E, Berg, D, Geisen, C, Friedrich, CM, Summers, P, Frangi, AF, State, MW, Wichmann, HE, Breteler, MMB, Wijmenga, C, Mane, S, Peltonen, L, Elio, V, Sturkenboom, MCJM, Lawford, P, Byrne, J, MacHo, J, Sandalcioglu, EI, Meyer, B, Raabe, A, Steinmetz, H, Rüfenacht, D, Jääskeläinen, JE, Hernesniemi, J, Rinkel, GJE, Zembutsu, H, Inoue, I, Palotie, A, Cambien, F, Nakamura, Y, Lifton, RP & Günel, M 2010, 'Genome-wide association study of intracranial aneurysm identifies three new risk loci', Nature Genetics, vol. 42, no. 5, pp. 420-425. https://doi.org/10.1038/ng.563

TY - JOUR

T1 - Genome-wide association study of intracranial aneurysm identifies three new risk loci

AU - Yasuno, Katsuhito

AU - Bilguvar, Kaya

AU - Bijlenga, Philippe

AU - Low, Siew Kee

AU - Krischek, Boris

AU - Auburger, Georg

AU - Simon, Matthias

AU - Krex, Dietmar

AU - Arlier, Zulfikar

AU - Nayak, Nikhil

AU - Ruigrok, Ynte M.

AU - Niemelä, Mika

AU - Tajima, Atsushi

AU - Von Und Zu Fraunberg, Mikael

AU - Dóczi, Tamás

AU - Wirjatijasa, Florentina

AU - Hata, Akira

AU - Blasco, Jordi

AU - Oszvald, Agi

AU - Kasuya, Hidetoshi

AU - Zilani, Gulam

AU - Schoch, Beate

AU - Singh, Pankaj

AU - Stüer, Carsten

AU - Risselada, Roelof

AU - Beck, Jürgen

AU - Sola, Teresa

AU - Ricciardi, Filomena

AU - Aromaa, Arpo

AU - Illig, Thomas

AU - Schreiber, Stefan

AU - Van Duijn, Cornelia M.

AU - Van Den Berg, Leonard H.

AU - Perret, Claire

AU - Proust, Carole

AU - Roder, Constantin

AU - Ozturk, Ali K.

AU - Gaál, Emília

AU - Berg, Daniela

AU - Geisen, Christof

AU - Friedrich, Christoph M.

AU - Summers, Paul

AU - Frangi, Alejandro F.

AU - State, Matthew W.

AU - Wichmann, H. Erich

AU - Breteler, Monique M.B.

AU - Wijmenga, Cisca

AU - Mane, Shrikant

AU - Peltonen, Leena

AU - Elio, Vivas

AU - Sturkenboom, Miriam C.J.M.

AU - Lawford, Patricia

AU - Byrne, James

AU - MacHo, Juan

AU - Sandalcioglu, Erol I.

AU - Meyer, Bernhard

AU - Raabe, Andreas

AU - Steinmetz, Helmuth

AU - Rüfenacht, Daniel

AU - Jääskeläinen, Juha E.

AU - Hernesniemi, Juha

AU - Rinkel, Gabriel J.E.

AU - Zembutsu, Hitoshi

AU - Inoue, Ituro

AU - Palotie, Aarno

AU - Cambien, François

AU - Nakamura, Yusuke

AU - Lifton, Richard P.

AU - Günel, Murat

N1 - Funding Information: We are grateful to the participants who made this study possible.We thank A. Chamberlain, B. Meseck-Selchow and members of the Keck Foundation Biotechnology Resource Laboratory for their technical help. This study was supported by the Yale Center for Human Genetics and Genomics and the Yale Program on Neurogenetics, the US National Institutes of Health (NIH) grants R01NS057756 (M.G.) and U24 NS051869 (S.M.) and the Howard Hughes Medical Institute (R.P.L.). This study is partially funded by the European Commission under the 6th Framework Programme through the @neurIST (www.aneurist.org) project under contract no. FP6-IST-2004-027703. The Frankfurt case cohort collection was supported by Bundesministerium für Bildung und Forschung (01GI9907), Utrecht Control cohort by the Prinses Beatrix Fonds and the Adessium foundation (L.H.v.d.B.). S.M. was supported in part by the Clinical and Translational Science Award UL1 RR024139, National Center for Research Resources, NIH.We would also like to acknowledge the use of Yale University Biomedical High Performance Computing Center (NIH grant: RR19895).

PY - 2010/5

Y1 - 2010/5

N2 - Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,891 cases and 14,181 controls with 832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 18q11.2 (odds ratio (OR) = 1.22, P = 1.1 × 10 12), STARD13-KL on 13q13.1 (OR = 1.20, P = 2.5 × 10 9) and a gene-rich region on 10q24.32 (OR = 1.29, P = 1.2 × 10 9). We also confirmed prior associations near SOX17 (8q11.23-q12.1; OR = 1.28, P = 1.3 × 10 12) and CDKN2A-CDKN2B (9p21.3; OR = 1.31, P = 1.5 × 10 22). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair.

AB - Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,891 cases and 14,181 controls with 832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 18q11.2 (odds ratio (OR) = 1.22, P = 1.1 × 10 12), STARD13-KL on 13q13.1 (OR = 1.20, P = 2.5 × 10 9) and a gene-rich region on 10q24.32 (OR = 1.29, P = 1.2 × 10 9). We also confirmed prior associations near SOX17 (8q11.23-q12.1; OR = 1.28, P = 1.3 × 10 12) and CDKN2A-CDKN2B (9p21.3; OR = 1.31, P = 1.5 × 10 22). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair.

UR - https://www.scopus.com/pages/publications/77951768060

U2 - 10.1038/ng.563

DO - 10.1038/ng.563

M3 - Article

C2 - 20364137

AN - SCOPUS:77951768060

SN - 1061-4036

VL - 42

SP - 420

EP - 425

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

Genome-wide association study of intracranial aneurysm identifies three new risk loci

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