Genome-wide association study of intracranial aneurysm identifies three new risk loci.
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.
Yasuno
Katsuhito
K
Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA.
Bilguvar
Kaya
K
Bijlenga
Philippe
P
Low
Siew-Kee
SK
Krischek
Boris
B
Auburger
Georg
G
Simon
Matthias
M
Krex
Dietmar
D
Arlier
Zulfikar
Z
Nayak
Nikhil
N
Ruigrok
Ynte M
YM
Niemelä
Mika
M
Tajima
Atsushi
A
von und zu Fraunberg
Mikael
M
Dóczi
Tamás
T
Wirjatijasa
Florentina
F
Hata
Akira
A
Blasco
Jordi
J
Oszvald
Agi
A
Kasuya
Hidetoshi
H
Zilani
Gulam
G
Schoch
Beate
B
Singh
Pankaj
P
Stüer
Carsten
C
Risselada
Roelof
R
Beck
Jürgen
J
Sola
Teresa
T
Ricciardi
Filomena
F
Aromaa
Arpo
A
Illig
Thomas
T
Schreiber
Stefan
S
van Duijn
Cornelia M
CM
van den Berg
Leonard H
LH
Perret
Claire
C
Proust
Carole
C
Roder
Constantin
C
Ozturk
Ali K
AK
Gaál
Emília
E
Berg
Daniela
D
Geisen
Christof
C
Friedrich
Christoph M
CM
Summers
Paul
P
Frangi
Alejandro F
AF
State
Matthew W
MW
Wichmann
H Erich
HE
Breteler
Monique M B
MM
Wijmenga
Cisca
C
Mane
Shrikant
S
Peltonen
Leena
L
Elio
Vivas
V
Sturkenboom
Miriam C J M
MC
Lawford
Patricia
P
Byrne
James
J
Macho
Juan
J
Sandalcioglu
Erol I
EI
Meyer
Bernhard
B
Raabe
Andreas
A
Steinmetz
Helmuth
H
Rüfenacht
Daniel
D
Jääskeläinen
Juha E
JE
Hernesniemi
Juha
J
Rinkel
Gabriel J E
GJ
Zembutsu
Hitoshi
H
Inoue
Ituro
I
Palotie
Aarno
A
Cambien
François
F
Nakamura
Yusuke
Y
Lifton
Richard P
RP
Günel
Murat
M
D002453:Cell Cycle; D049109:Cell Proliferation; D015331:Cohort Studies; D005060:Europe; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006470:Hemorrhage / Q000235:genetics; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics*; D007564:Japan; D008297:Male; D008957:Models, Genetic; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide