title: Susceptibility loci for intracranial aneurysm in European and Japanese populations.
abstract: Stroke is the world's third leading cause of death. One cause of stroke, intracranial aneurysm, affects approximately 2% of the population and accounts for 500,000 hemorrhagic strokes annually in mid-life (median age 50), most often resulting in death or severe neurological impairment. The pathogenesis of intracranial aneurysm is unknown, and because catastrophic hemorrhage is commonly the first sign of disease, early identification is essential. We carried out a multistage genome-wide association study (GWAS) of Finnish, Dutch and Japanese cohorts including over 2,100 intracranial aneurysm cases and 8,000 controls. Genome-wide genotyping of the European cohorts and replication studies in the Japanese cohort identified common SNPs on chromosomes 2q, 8q and 9p that show significant association with intracranial aneurysm with odds ratios 1.24-1.36. The loci on 2q and 8q are new, whereas the 9p locus was previously found to be associated with arterial diseases, including intracranial aneurysm. Associated SNPs on 8q likely act via SOX17, which is required for formation and maintenance of endothelial cells, suggesting a role in development and repair of the vasculature; CDKN2A at 9p may have a similar role. These findings have implications for the pathophysiology, diagnosis and therapy of intracranial aneurysm.
authors.affiliation: Department of Neurosurgery, Neurobiology, Yale Center for Human Genetics and Genomics, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Kaya
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authors.lastname: Bilguvar
authors.forename: Katsuhito
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authors.lastname: Yasuno
authors.forename: Mika
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authors.lastname: Niemelä
authors.forename: Ynte M
authors.initials: YM
authors.lastname: Ruigrok
authors.forename: Mikael
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authors.lastname: von Und Zu Fraunberg
authors.forename: Cornelia M
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authors.lastname: van Duijn
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authors.initials: LH
authors.lastname: van den Berg
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authors.lastname: Mane
authors.forename: Christopher E
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authors.lastname: Gaál
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authors.lastname: Bayri
authors.forename: Luis
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authors.lastname: Kolb
authors.forename: Zulfikar
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authors.lastname: Arlier
authors.forename: Sudhakar
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authors.lastname: Ravuri
authors.forename: Antti
authors.initials: A
authors.lastname: Ronkainen
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tajima
authors.forename: Aki
authors.initials: A
authors.lastname: Laakso
authors.forename: Akira
authors.initials: A
authors.lastname: Hata
authors.forename: Hidetoshi
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authors.lastname: Kasuya
authors.forename: Timo
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authors.lastname: Koivisto
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authors.lastname: Rinne
authors.forename: Juha
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authors.forename: Monique M B
authors.initials: MM
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authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Matthew W
authors.initials: MW
authors.lastname: State
authors.forename: Gabriel J E
authors.initials: GJ
authors.lastname: Rinkel
authors.forename: Juha
authors.initials: J
authors.lastname: Hernesniemi
authors.forename: Juha E
authors.initials: JE
authors.lastname: Jääskeläinen
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.forename: Ituro
authors.initials: I
authors.lastname: Inoue
authors.forename: Richard P
authors.initials: RP
authors.lastname: Lifton
authors.forename: Murat
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authors.lastname: Günel
mesh_terms: D044466:Asian People / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D002532:Intracranial Aneurysm / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics