Susceptibility loci for intracranial aneurysm in European and Japanese populations.
Susceptibility loci for intracranial aneurysm in European and Japanese populations.
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DOI：
10.1038/ng.240
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发表时间：
2008-12
期刊：
影响因子：
30.8
通讯作者：
Guenel, Murat
中科院分区：
文献类型：
--
作者：
Bilguvar, Kaya;Yasuno, Katsuhito;Niemela, Mika;Ruigrok, Ynte M.;Fraunberg, Mikael von und zu;van Duijn, Cornelia M.;van den Berg, Leonard H.;Mane, Shrikant;Mason, Christopher E.;Choi, Murim;Gaal, Emilia;Bayri, Yasar;Kolb, Luis;Arlier, Zulfikar;Ravuri, Sudhakar;Ronkainen, Antti;Tajima, Atsushi;Laakso, Aki;Hata, Akira;Kasuya, Hidetoshi;Koivisto, Timo;Rinne, Jaakko;Ohman, Juha;Breteler, Monique M. B.;Wijmenga, Cisca;State, Matthew W.;Rinkel, Gabriel J. E.;Hernesniemi, Juha;Jaaskelainen, Juha E.;Palotie, Aarno;Inoue, Ituro;Lifton, Richard P.;Guenel, Murat
中风是世界上第三大死因。脑卒中的一个原因是颅内动脉瘤，约影响2%的人口，每年在中年（中位年龄50岁）发生50万例出血性中风，最常导致死亡或严重的神经损伤。颅内动脉瘤的发病机制尚不清楚，由于灾难性出血通常是疾病的第一个征兆，因此早期识别至关重要。我们对芬兰、荷兰和日本的队列进行了一项多阶段全基因组关联研究（GWAS），包括2100多例颅内动脉瘤病例和8000例对照。欧洲队列的全基因组基因分型和日本队列的复制研究发现染色体2q、8q和9p上的常见snp与颅内动脉瘤有显著关联，比值比为1.24-1.36。2q和8q位点是新发现的，而9p位点以前被发现与动脉疾病有关，包括颅内动脉瘤。8q上的相关snp可能通过SOX17起作用，这是内皮细胞形成和维持所必需的，表明在血管系统的发育和修复中起作用；CDKN2A在9p位点可能有类似的作用。这些发现对颅内动脉瘤的病理生理学、诊断和治疗具有一定的指导意义。
Stroke is the world’s third leading cause of death. One cause of stroke, intracranial aneurysm, affects ~2% of the population and accounts for 500,000 hemorrhagic strokes annually in midlife (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.
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影响因子：
30.8
作者：
Zeggini, Eleftheria;Scott, Laura J.;Saxena, Richa;Voight, Benjamin F.;Marchini, Jonathan L.;Hu, Tianle;de Bakker, Paul I. W.;Abecasis, Goncalo R.;Almgren, Peter;Andersen, Gitte;Ardlie, Kristin;Bostroem, Kristina Bengtsson;Bergman, Richard N.;Bonnycastle, Lori L.;Borch-Johnsen, Knut;Burtt, Noel P.;Chen, Hong;Chines, Peter S.;Daly, Mark J.;Deodhar, Parimal;Ding, Chia-Jen;Doney, Alex S. F.;Duren, William L.;Elliott, Katherine S.;Erdos, Michael R.;Frayling, Timothy M.;Freathy, Rachel M.;Gianniny, Lauren;Grallert, Harald;Grarup, Niels;Groves, Christopher J.;Guiducci, Candace;Hansen, Torben;Herder, Christian;Hitman, Graham A.;Hughes, Thomas E.;Isomaa, Bo;Jackson, Anne U.;Jorgensen, Torben;Kong, Augustine;Kubalanza, Kari;Kuruvilla, Finny G.;Kuusisto, Johanna;Langenberg, Claudia;Lango, Hana;Lauritzen, Torsten;Li, Yun;Lindgren, Cecilia M.;Lyssenko, Valeriya;Marvelle, Amanda F.;Meisinger, Christa;Midthjell, Kristian;Mohlke, Karen L.;Morken, Mario A.;Morris, Andrew D.;Narisu, Narisu;Nilsson, Peter;Owen, Katharine R.;Palmer, Colin N. A.;Payne, Felicity;Perry, John R. B.;Pettersen, Elin;Platou, Carl;Prokopenko, Inga;Qi, Lu;Qin, Li;Rayner, Nigel W.;Rees, Matthew;Roix, Jeffrey J.;Sandbaek, Anelli;Shields, Beverley;Sjogren, Marketa;Steinthorsdottir, Valgerdur;Stringham, Heather M.;Swift, Amy J.;Thorleifsson, Gudmar;Thorsteinsdottir, Unnur;Timpson, Nicholas J.;Tuomi, Tiinamaija;Tuomilehto, Jaakko;Walker, Mark;Watanabe, Richard M.;Weedon, Michael N.;Willer, Cristen J.;Illig, Thomas;Hveem, Kristian;Hu, Frank B.;Laakso, Markku;Stefansson, Kari;Pedersen, Oluf;Wareham, Nicholas J.;Barroso, Ines;Hattersley, Andrew T.;Collins, Francis S.;Groop, Leif;McCarthy, Mark I.;Boehnke, Michael;Altshuler, David
通讯作者：
Altshuler, David
影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
8.3
作者：
Foroud, Tatiana;Sauerbeck, Laura;Broderick, Joseph P.
通讯作者：
Broderick, Joseph P.
影响因子：
64.8
作者：
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通讯作者：
Skol, Andrew
影响因子：
30.8
作者：
Helgadottir, Anna;Thorleifsson, Gudmar;Stefansson, Kari
通讯作者：
Stefansson, Kari