Susceptibility loci for intracranial aneurysm in European and Japanese populations.
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.
Bilguvar
Kaya
K
Department of Neurosurgery, Neurobiology, Yale Center for Human Genetics and Genomics, Yale University School of Medicine, New Haven, CT 06510, USA.
Yasuno
Katsuhito
K
Niemelä
Mika
M
Ruigrok
Ynte M
YM
von Und Zu Fraunberg
Mikael
M
van Duijn
Cornelia M
CM
van den Berg
Leonard H
LH
Mane
Shrikant
S
Mason
Christopher E
CE
Choi
Murim
M
Gaál
Emília
E
Bayri
Yasar
Y
Kolb
Luis
L
Arlier
Zulfikar
Z
Ravuri
Sudhakar
S
Ronkainen
Antti
A
Tajima
Atsushi
A
Laakso
Aki
A
Hata
Akira
A
Kasuya
Hidetoshi
H
Koivisto
Timo
T
Rinne
Jaakko
J
Ohman
Juha
J
Breteler
Monique M B
MM
Wijmenga
Cisca
C
State
Matthew W
MW
Rinkel
Gabriel J E
GJ
Hernesniemi
Juha
J
Jääskeläinen
Juha E
JE
Palotie
Aarno
A
Inoue
Ituro
I
Lifton
Richard P
RP
Günel
Murat
M
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