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