Genome-wide association study of intracranial aneurysm identifies three new risk loci

被引：220

作者：

Yasuno, Katsuhito ^{[1
,2
,3
]}

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

Bijlenga, Philippe ^{[4
]}

Low, Siew-Kee ^{[5
]}

Krischek, Boris ^{[6
]}

Auburger, Georg ^{[7
]}

Simon, Matthias ^{[8
]}

Krex, Dietmar ^{[9
]}

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

Nayak, Nikhil ^{[1
,2
,3
]}

Ruigrok, Ynte M. ^{[10
]}

Niemelaa, Mika ^{[11
]}

Tajima, Atsushi ^{[12
]}

Fraunberg, Mikael von Und Zu ^{[13
]}

Doczi, Tamas ^{[14
]}

Wirjatijasa, Florentina ^{[7
]}

Hata, Akira ^{[15
]}

Blasco, Jordi ^{[16
]}

Oszvald, Agi ^{[17
]}

Kasuya, Hidetoshi ^{[18
]}

Zilani, Gulam ^{[19
]}

Schoch, Beate ^{[20
]}

Singh, Pankaj ^{[21
,22
]}

Stueer, Carsten ^{[23
]}

Risselada, Roelof ^{[24
]}

Beck, Juergen ^{[17
]}

Sola, Teresa ^{[25
]}

Ricciardi, Filomena ^{[7
]}

Aromaa, Arpo ^{[26
]}

Illig, Thomas ^{[27
]}

Schreiber, Stefan ^{[28
]}

van Duijn, Cornelia M. ^{[29
,30
]}

van den Berg, Leonard H. ^{[10
]}

Perret, Claire ^{[31
]}

Proust, Carole ^{[31
]}

Roder, Constantin ^{[6
]}

Ozturk, Ali K. ^{[1
,2
,3
]}

Gaal, Emilia ^{[1
,2
,3
,11
]}

Berg, Daniela ^{[32
,33
]}

Geisen, Christof ^{[34
]}

Friedrich, Christoph M. ^{[35
]}

Summers, Paul ^{[19
]}

Frangi, Alejandro F. ^{[36
,37
,38
]}

State, Matthew W. ^{[1
,39
,40
]}

Wichmann, H. Erich ^{[27
]}

Breteler, Monique M. B. ^{[29
,30
]}

Wijmenga, Cisca ^{[41
,42
]}

Mane, Shrikant ^{[43
]}

Peltonen, Leena ^{[44
,45
]}

Elio, Vivas ^{[25
]}

机构：

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

[2] Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06510 USA

[3] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06510 USA

[4] Univ Hosp Geneva, Serv Neurochirurg, Dept Clin Neurosci, Geneva, Switzerland

[5] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Tokyo, Japan

[6] Univ Tubingen, Dept Neurosurg, Tubingen, Germany

[7] Goethe Univ Frankfurt, Dept Neurol, Frankfurt, Germany

[8] Univ Bonn, Dept Neurosurg, D-5300 Bonn, Germany

[9] Tech Univ Dresden, Carl Gustav Carus Univ Hosp Dresden, Dept Neurosurg, D-8027 Dresden, Germany

[10] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurol, Utrecht, Netherlands

[11] Univ Helsinki, Cent Hosp, Dept Neurosurg, Helsinki, Finland

[12] Tokai Univ, Sch Med, Div Mol Life Sci, Kanagawa 2591100, Japan

[13] Kuopio Univ Hosp, Dept Neurosurg, SF-70210 Kuopio, Finland

[14] Univ Pecs, Sch Med, Pecs, Hungary

[15] Chiba Univ, Sch Med, Dept Publ Hlth, Chiba 280, Japan

[16] Hosp Clin Barcelona, Dept Vasc Radiol, Barcelona, Spain

[17] Goethe Univ Frankfurt, Dept Neurosurg, Frankfurt, Germany

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

[19] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Surg, Oxford OX3 9DU, England

[20] Univ Hosp, Dept Neurosurg, Essen, Germany

[21] Univ Sheffield, Med Phys Grp, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England

[22] Royal Hallamshire Hosp, Dept Neurosurg, Sheffield S10 2JF, S Yorkshire, England

[23] Tech Univ Munich, Dept Neurosurg, Munich, Germany

[24] Erasmus Univ, Med Ctr, Dept Med Informat, Rotterdam, Netherlands

[25] Hosp Gen Cataluna, San Cugat Del Valles, Spain

[26] Natl Publ Hlth Inst, Dept Hlth & Funct Capac, Helsinki, Finland

[27] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol, Munich, Germany

[28] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany

[29] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands

[30] Netherlands Consortium Hlth Aging, Rotterdam, Netherlands

[31] Univ Paris 06, INSERM, UMR S937, Paris, France

[32] Univ Tubingen, Dept Neurodegenerat, Ctr Neurol, Tubingen, Germany

[33] Univ Tubingen, Hertie Inst Clin Brain Res, Tubingen, Germany

[34] Deutsch Rotes Kreuz Blood Donor Serv Baden Wuertt, Dept Mol Haemostasis, Inst Transfus Med & Immunohaematol, Frankfurt, Germany

[35] Fraunhofer Inst Algorithms & Sci Comp, St Augustin, Germany

[36] Univ Pompeu Fabra, Barcelona, Spain

[37] Networking Biomed Res Ctr Bioengn Biomat & Nanome, Barcelona, Spain

[38] ICREA, Barcelona, Spain

[39] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA

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

[41] Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands

[42] Univ Groningen, Groningen, Netherlands

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

[44] Wellcome Trust Sanger Inst, Cambridge, England

[45] Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland

[46] Clin Hirslanden, Swiss Neuro Inst, Dept Neuroradiol, Zurich, Switzerland

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

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

来源：

NATURE GENETICS | 2010年 / 42卷 / 05期

基金：

美国国家卫生研究院;

关键词：

POPULATION-STRUCTURE; IMPUTATION; PROBABILITY; PREVALENCE; DESIGNS; FALSE; BIAS;

D O I：

10.1038/ng.563

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 similar to 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.

引用

页码：420 / U69

页数：8

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