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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Katsuhito Yasuno - , Yale University (Author)
  • Kaya Bilguvar - , Yale University (Author)
  • Philippe Bijlenga - , University of Geneva (Author)
  • Siew Kee Low - , The University of Tokyo (Author)
  • Boris Krischek - , University of Tübingen (Author)
  • Georg Auburger - , University Hospital Frankfurt (Author)
  • Matthias Simon - , University of Bonn (Author)
  • Dietmar Krex - , Department of Neurosurgery, Dresden University of Technology (Author)
  • Zulfikar Arlier - , Yale University (Author)
  • Nikhil Nayak - , Yale University (Author)
  • Ynte M. Ruigrok - , Utrecht University (Author)
  • Mika Niemelä - , University of Helsinki (Author)
  • Atsushi Tajima - , Tokai University (Author)
  • Mikael Von Und Zu Fraunberg - , University of Eastern Finland (Author)
  • Tamás Dóczi - , University of Pecs (Author)
  • Florentina Wirjatijasa - , University Hospital Frankfurt (Author)
  • Akira Hata - , Chiba University (Author)
  • Jordi Blasco - , University of Barcelona (Author)
  • Agi Oszvald - , University Hospital Frankfurt (Author)
  • Hidetoshi Kasuya - , Tokyo Women's Medical University (Author)
  • Gulam Zilani - , University of Oxford (Author)
  • Beate Schoch - , University of Duisburg-Essen (Author)
  • Pankaj Singh - , University of Sheffield, Royal Hallamshire Hospital (Author)
  • Carsten Stüer - , Technical University of Munich (Author)
  • Roelof Risselada - , Erasmus University Rotterdam (Author)
  • Jürgen Beck - , University Hospital Frankfurt (Author)
  • Teresa Sola - , Hospital General de Catalunya (Author)
  • Filomena Ricciardi - , University Hospital Frankfurt (Author)
  • Arpo Aromaa - , National Institute for Health and Welfare (Author)
  • Thomas Illig - , Helmholtz Centre for Environmental Research (Author)
  • Stefan Schreiber - , Kiel University (Author)
  • Cornelia M. Van Duijn - , Erasmus University Rotterdam, Netherlands Consortium for Health Aging (Author)
  • Leonard H. Van Den Berg - , Utrecht University (Author)
  • Claire Perret - , Sorbonne Université (Author)
  • Carole Proust - , Sorbonne Université (Author)
  • Constantin Roder - , University of Tübingen (Author)
  • Ali K. Ozturk - , Yale University (Author)
  • Emília Gaál - , Yale University, University of Helsinki (Author)
  • Daniela Berg - , University of Tübingen (Author)
  • Christof Geisen - , German Red Cross (Author)
  • Christoph M. Friedrich - , Fraunhofer Institute for Algorithms and Scientific Computing (Author)
  • Paul Summers - , University of Oxford (Author)
  • Alejandro F. Frangi - , Pompeu Fabra University, CIBER - Center for Biomedical Research Network, ICREA (Author)
  • Matthew W. State - , Yale University (Author)
  • H. Erich Wichmann - , Helmholtz Centre for Environmental Research (Author)
  • Monique M.B. Breteler - , Erasmus University Rotterdam, Netherlands Consortium for Health Aging (Author)
  • Cisca Wijmenga - , University of Groningen (Author)
  • Shrikant Mane - , Yale University (Author)
  • Leena Peltonen - , Wellcome Sanger Institute, University of Helsinki (Author)
  • Vivas Elio - , Hospital General de Catalunya (Author)
  • Miriam C.J.M. Sturkenboom - , Erasmus University Rotterdam (Author)
  • Patricia Lawford - , University of Sheffield (Author)
  • James Byrne - , University of Oxford (Author)
  • Juan MacHo - , University of Barcelona (Author)
  • Erol I. Sandalcioglu - , University of Duisburg-Essen (Author)
  • Bernhard Meyer - , Technical University of Munich (Author)
  • Andreas Raabe - , University Hospital Frankfurt (Author)
  • Helmuth Steinmetz - , University Hospital Frankfurt (Author)
  • Daniel Rüfenacht - , University of Geneva, Klinik Hirslanden (Author)
  • Juha E. Jääskeläinen - , University of Eastern Finland (Author)
  • Juha Hernesniemi - , University of Helsinki (Author)
  • Gabriel J.E. Rinkel - , Utrecht University (Author)
  • Hitoshi Zembutsu - , The University of Tokyo (Author)
  • Ituro Inoue - , Tokai University (Author)
  • Aarno Palotie - , Wellcome Sanger Institute, University of Helsinki (Author)
  • François Cambien - , Sorbonne Université (Author)
  • Yusuke Nakamura - , The University of Tokyo (Author)
  • Richard P. Lifton - , Yale University (Author)
  • Murat Günel - , Yale University (Author)

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.

Details

Original languageEnglish
Pages (from-to)420-425
Number of pages6
JournalNature Genetics
Volume42
Issue number5
Publication statusPublished - May 2010
Peer-reviewedYes

External IDs

Scopus 77951768060
PubMed 20364137

Keywords

ASJC Scopus subject areas