Scientific article
OA Policy
English

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

Published inNature genetics, vol. 42, no. 5, p. 420-425
Publication date2010-05
First online date2010-04-04
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 approximately 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 x 10(-12)), STARD13-KL on 13q13.1 (OR = 1.20, P = 2.5 x 10(-9)) and a gene-rich region on 10q24.32 (OR = 1.29, P = 1.2 x 10(-9)). We also confirmed prior associations near SOX17 (8q11.23-q12.1; OR = 1.28, P = 1.3 x 10(-12)) and CDKN2A-CDKN2B (9p21.3; OR = 1.31, P = 1.5 x 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.

Keywords
  • Cell Cycle
  • Cell Proliferation
  • Cohort Studies
  • Europe
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Hemorrhage / genetics
  • Humans
  • Intracranial Aneurysm / genetics
  • Japan
  • Male
  • Models, Genetic
  • Odds Ratio
  • Polymorphism, Single Nucleotide
Funding
  • NINDS NIH HHS [R01 NS057756-03]
  • NCRR NIH HHS [RR19895]
  • Wellcome Trust [089062]
  • Howard Hughes Medical Institute
Citation (ISO format)
YASUNO, Katsuhito et al. Genome-wide association study of intracranial aneurysm identifies three new risk loci. In: Nature genetics, 2010, vol. 42, n° 5, p. 420–425. doi: 10.1038/ng.563
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Article (Published version)
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Article (Accepted version)
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Identifiers
Additional URL for this publicationhttps://www.nature.com/articles/ng.563
Journal ISSN1061-4036
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