Replication of restless legs syndrome loci in three European populations.
Replication of restless legs syndrome loci in three European populations.
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DOI：
10.1136/jmg.2008.062992
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发表时间：
2009-05
影响因子：
4
通讯作者：
Winkelmann J
中科院分区：
文献类型：
--
作者：
Kemlink D;Polo O;Frauscher B;Gschliesser V;Högl B;Poewe W;Vodicka P;Vavrova J;Sonka K;Nevsimalova S;Schormair B;Lichtner P;Silander K;Peltonen L;Gieger C;Wichmann HE;Zimprich A;Roeske D;Müller-Myhsok B;Meitinger T;Winkelmann J
不宁腿综合征（RLS）与染色体2 p、6p和15 q上MEIS 1、BTBD 9和MAP 2K 5/LBXCOR 1的三个内含子和基因间区域的常见变异相关。我们的研究调查了来自捷克共和国（290例病例和450例对照），奥地利（269例病例和611例对照）和芬兰（90例病例和169例对照）的649例RLS患者和1230例对照的这些变异。根据先前全基因组扫描的结果，选择了三个基因组区域内的十个单核苷酸多态性（SNP）。使用Sequenom平台对样品进行基因分型。我们在合并样本集中复制了所有基因座的相关性（MEIS 1中的rs 2300478，p = 1.26×10−5，比值比（OR）= 1.47，BTBD 9中的rs3923809，p = 4.11×10−5，OR = 1.58，MAP 2K 5/LBXCOR 1中的rs6494696，p = 0.04764，OR = 1.27）。仅对所有对照组的家族性病例进行分析，所有三个位点均显著相关。仅使用散发病例，我们可以确认仅与BTBD 9相关。我们的研究表明，这三个基因座的变异赋予欧洲血统患者一致的疾病风险。在已知的基因座中，BTBD 9似乎在其对不同人群的RLS的影响方面最一致，并且也最不依赖于家族聚集。
Restless legs syndrome (RLS) is associated with common variants in three intronic and intergenic regions in MEIS1, BTBD9, and MAP2K5/LBXCOR1 on chromosomes 2p, 6p and 15q. Our study investigated these variants in 649 RLS patients and 1230 controls from the Czech Republic (290 cases and 450 controls), Austria (269 cases and 611 controls) and Finland (90 cases and 169 controls). Ten single nucleotide polymorphisms (SNPs) within the three genomic regions were selected according to the results of previous genome-wide scans. Samples were genotyped using Sequenom platforms. We replicated associations for all loci in the combined samples set (rs2300478 in MEIS1, p = 1.26×10−5, odds ratio (OR) = 1.47, rs3923809 in BTBD9, p = 4.11×10−5, OR = 1.58 and rs6494696 in MAP2K5/LBXCOR1, p = 0.04764, OR = 1.27). Analysing only familial cases against all controls, all three loci were significantly associated. Using sporadic cases only, we could confirm the association only with BTBD9. Our study shows that variants in these three loci confer consistent disease risks in patients of European descent. Among the known loci, BTBD9 seems to be the most consistent in its effect on RLS across populations and is also most independent of familial clustering.
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影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
9.8
作者：
Pichler, Irene;Marroni, Fabio;Pramstaller, Peter P.
通讯作者：
Pramstaller, Peter P.
影响因子：
8.6
作者：
Winkelmann, J;Lichtner, P;Muller-Myhsok, B
通讯作者：
Muller-Myhsok, B
影响因子：
2.2
作者：
Kemlink, David;Plazzi, Giuseppe;Montagna, Pasquale
通讯作者：
Montagna, Pasquale
影响因子：
11.2
作者：
Levchenko, A;Montplaisir, JY;Rouleau, GA
通讯作者：
Rouleau, GA