Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7

Tatiana Foroud, Dongbing Lai, Daniel Koller, Femke Van't Hof, Mitja I. Kurki, Craig S. Anderson, Robert D. Brown, Edward Sander Connolly, Johan G. Eriksson, Matthew Flaherty, Myriam Fornage, Mikael Von Und Zu Fraunberg, Emília I. Gaál, Aki Laakso, Juha Hernesniemi, John Huston, Juha E. Jääskeläinen, Lambertus A. Kiemeney, Riku Kivisaari, Dawn KleindorferNerissa Ko, Hanna Lehto, Jason Mackey, Irene Meissner, Charles J. Moomaw, Thomas H. Mosley, Marek Moskala, Mika Niemelä, Aarno Palotie, Joanna Pera, Gabriel Rinkel, Stephan Ripke, Guy Rouleau, Ynte Ruigrok, Laura Sauerbeck, Agnieszka Słowik, Sita H. Vermeulen, Daniel Woo, Bradford B. Worrall, Joseph Broderick

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Background and Purpose-Common variants have been identified using genome-wide association studies which contribute to intracranial aneurysms (IA) susceptibility. However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk. Methods-Initial analysis was performed in a discovery sample of 2617 IA cases and 2548 controls of white ancestry. Novel chromosomal regions meeting genome-wide significance were further tested for association in 2 independent replication samples: Dutch (717 cases; 3004 controls) and Finnish (799 cases; 2317 controls). A meta-analysis was performed to combine the results from the 3 studies for key chromosomal regions of interest. Results-Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P<1.0×10-11), in a gene previously associated with IA. A novel region on chromosome 7, near HDAC9, was associated with IA (rs10230207; P=4.14×10-8). This association replicated in the Dutch sample (P=0.01) but failed to show association in the Finnish sample (P=0.25). Meta-analysis results of the 3 cohorts reached statistical significant (P=9.91×10-10). Conclusions-We detected a novel region associated with IA susceptibility that was replicated in an independent Dutch sample. This region on chromosome 7 has been previously associated with ischemic stroke and the large vessel stroke occlusive subtype (including HDAC9), suggesting a possible genetic link between this stroke subtype and IA.

Original languageEnglish (US)
Pages (from-to)3194-3199
Number of pages6
JournalStroke
Volume45
Issue number11
DOIs
StatePublished - Jan 1 2014

Keywords

  • Chromosomes
  • Genome-wide association study
  • Human
  • Intracranial aneurysm
  • Pair 7

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Fingerprint Dive into the research topics of 'Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7'. Together they form a unique fingerprint.

  • Cite this

    Foroud, T., Lai, D., Koller, D., Van't Hof, F., Kurki, M. I., Anderson, C. S., Brown, R. D., Connolly, E. S., Eriksson, J. G., Flaherty, M., Fornage, M., Von Und Zu Fraunberg, M., Gaál, E. I., Laakso, A., Hernesniemi, J., Huston, J., Jääskeläinen, J. E., Kiemeney, L. A., Kivisaari, R., ... Broderick, J. (2014). Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7. Stroke, 45(11), 3194-3199. https://doi.org/10.1161/STROKEAHA.114.006096