Susceptibility loci for intracranial aneurysm in European and Japanese populations

被引：222

作者：

Bilguvar, Kaya ^{[1
,2
,3
]}

Yasuno, Katsuhito ^{[4
]}

Niemela, Mika ^{[5
]}

Ruigrok, Ynte M. ^{[6
]}

Fraunberg, Mikael von und zu ^{[7
]}

van Duijn, Cornelia M. ^{[8
,9
]}

van den Berg, Leonard H. ^{[6
]}

Mane, Shrikant ^{[10
]}

Mason, Christopher E. ^{[1
,11
]}

Choi, Murim ^{[1
]}

Gaal, Emilia ^{[1
,2
,3
,5
]}

Bayri, Yasar ^{[1
,2
,3
]}

Kolb, Luis ^{[1
,2
,3
]}

Arlier, Zulfikar ^{[1
,2
,3
]}

Ravuri, Sudhakar ^{[10
]}

Ronkainen, Antti ^{[7
]}

Tajima, Atsushi ^{[4
]}

Laakso, Aki ^{[5
]}

Hata, Akira ^{[12
]}

Kasuya, Hidetoshi ^{[13
]}

Koivisto, Timo ^{[7
]}

Rinne, Jaakko ^{[7
]}

Ohman, Juha ^{[14
]}

Breteler, Monique M. B. ^{[8
,9
]}

Wijmenga, Cisca ^{[15
,16
,17
]}

State, Matthew W. ^{[1
,11
]}

Rinkel, Gabriel J. E. ^{[6
]}

Hernesniemi, Juha ^{[5
]}

Jaaskelainen, Juha E. ^{[7
]}

Palotie, Aarno ^{[18
,19
]}

Inoue, Ituro

Lifton, Richard P. ^{[1
,20
,21
]}

Guenel, Murat ^{[1
,2
,3
]}

机构：

[1] Yale Univ, Sch Med, Yale Ctr Human Genet & Genom, Yale Program Neurogenet,Dept Genet, New Haven, CT 06510 USA

[2] Yale Univ, Sch Med, Yale Ctr Human Genet & Genom, Dept Neurosurg, New Haven, CT 06510 USA

[3] Yale Univ, Sch Med, Yale Ctr Human Genet & Genom, Dept Neurobiol, New Haven, CT 06510 USA

[4] Tokai Univ, Sch Med, Div Mol Life Sci, Kanagawa 2591193, Japan

[5] Univ Helsinki, Cent Hosp, Dept Neurosurg, FI-00029 Helsinki, Hus, Finland

[6] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurol, NL-3584 CX Utrecht, Netherlands

[7] Kuopio Univ Hosp, Dept Neurosurg, FI-70211 Kuopio, Finland

[8] Erasmus MC, Dept Epidemiol & Biostat, Genet Epidemiol Unit, NL-3000 CA Rotterdam, Netherlands

[9] Erasmus MC, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands

[10] Yale Univ, Keck Fdn Biotechnol Resource Lab, New Haven, CT 06510 USA

[11] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA

[12] Chiba Univ, Sch Med, Dept Publ Hlth, Chiba 2608670, Japan

[13] Tokyo Womens Univ, Med Ctr E, Dept Neurosurg, Tokyo 1168567, Japan

[14] Tampere Univ Hosp, Dept Neurosurg, Tampere 33521, Finland

[15] Univ Med Ctr Utrecht, Dept Biomed Genet, Complex Genet Sect, NL-3508 AB Utrecht, Netherlands

[16] Univ Med Ctr Groningen, Dept Genet, NL-9700 RR Groningen, Netherlands

[17] Univ Groningen, NL-9700 RR Groningen, Netherlands

[18] Univ Helsinki, Res Program Mol Med, Helsinki, Finland

[19] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England

[20] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA

[21] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA

来源：

NATURE GENETICS | 2008年 / 40卷 / 12期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/ng.240

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Stroke is the world's third leading cause of death. One cause of stroke, intracranial aneurysm, affects similar to 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(1). 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(2-5). Associated SNPs on 8q likely act via SOX17, which is required for formation and maintenance of endothelial cells(6-8), suggesting a role in development and repair of the vasculature; CDKN2A at 9p may have a similar role(9). These findings have implications for the pathophysiology, diagnosis and therapy of intracranial aneurysm.

引用

页码：1472 / 1477

页数：6

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