IL12A, MPHOSPH9/CDK2AP1 and RGS1 are novel multiple sclerosis susceptibility loci.
IL12A, MPHOSPH9/CDK2AP1 and RGS1 are novel multiple sclerosis susceptibility loci.
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DOI：
10.1038/gene.2010.28
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发表时间：
2010-07
影响因子：
5
通讯作者：
De Jager, P. L.
中科院分区：
文献类型：
--
作者：
Esposito, F.;Patsopoulos, N. A.;Cepok, S.;Kockum, I.;Leppa, V.;Booth, D. R.;Heard, R. N.;Stewart, G. J.;Cox, M.;Scott, R. J.;Lechner-Scott, J.;Goris, A.;Dobosi, R.;Dubois, B.;Rioux, J. D.;Oturai, A. B.;Sondergaard, H. B.;Sellebjerg, F.;Sorensen, P. S.;Reunanen, M.;Koivisto, K.;Cournu-Rebeix, I.;Fontaine, B.;Winkelmann, J.;Gieger, C.;Infante-Duarte, C.;Zipp, F.;Bergamaschi, L.;Leone, M.;Bergamaschi, R.;Cavalla, P.;Lorentzen, A. R.;Mero, I-L;Celius, E. G.;Harbo, H. F.;Spurkland, A.;Comabella, M.;Brynedal, B.;Alfredsson, L.;Bernardinelli, L.;Robertson, N. P.;Hawkins, C. P.;Barcellos, L. F.;Beecham, G.;Bush, W.;Cree, B. A. C.;Daly, M. J.;Ivinson, A. J.;Aubin, C.;Compston, A.;D'Alfonso, S.;Haines, J. L.;Hauser, S. L.;Hemmer, B.;Hillert, J.;McCauley, J. L.;Oksenberg, J.;Olsson, T.;Palotie, A.;Peltonen, L.;Pericak-Vance, M. A.;Saarela, J.;Sawcer, S. J.;Stranger, B.;Boneschi, F. M.;Comi, G.;Hafler, D. A.;de Bakker, P. I. W.;De Jager, P. L.
最近的一项荟萃分析发现了七个单核苷酸多态(SNPs)，这些SNPs具有与多发性硬化症(MS)相关的提示证据。我们报告了一项复制研究中对这些多态的分析，该研究包括8,085例病例和7,777名对照。执行了跨复制集合的荟萃分析和与发现数据集的联合分析。使用RNA表达数据来探索验证的易感基因座可能的功能后果。对于所有测试的SNPs，在复制阶段观察到的影响涉及相同的等位基因，在发现阶段观察到的影响方向相同。在联合分析中，RGS1(P值=3.55×10-9)、IL12A(P=3.08×10-8)和MPHOSPH9/CDK2AP1(P=3.96×10-8)三个座位超过了全基因组意义。RGS1风险等位基因与乳糜泻(CD)是相同的，而IL12A风险等位基因似乎对乳糜泻具有保护作用。在MPHOSPH9/CDK2AP1基因座上，危险等位基因与细胞周期调节因子CDK2AP1的RNA表达降低相关；这种影响在淋巴母细胞系(P=1.18×10-5)和MS患者的外周血单核细胞(P=0.01)中都可以看到。因此，我们报告了三个新的MS易感基因，其中包括一个可能影响自身反应性细胞增殖的新的炎症性疾病基因。
A recent meta-analysis identified seven single-nucleotide polymorphisms (SNPs) with suggestive evidence of association with multiple sclerosis (MS). We report an analysis of these polymorphisms in a replication study that includes 8,085 cases and 7,777 controls. A meta-analysis across the replication collections and a joint analysis with the discovery data set were performed. The possible functional consequences of the validated susceptibility loci were explored using RNA expression data. For all of the tested SNPs, the effect observed in the replication phase involved the same allele and the same direction of effect observed in the discovery phase. Three loci exceeded genome-wide significance in the joint analysis: RGS1 (P value = 3.55 × 10–9), IL12A (P = 3.08 × 10–8) and MPHOSPH9/CDK2AP1 (P = 3.96 × 10–8). The RGS1 risk allele is shared with celiac disease (CD), and the IL12A risk allele seems to be protective for celiac disease. Within the MPHOSPH9/CDK2AP1 locus, the risk allele correlates with diminished RNA expression of the cell cycle regulator CDK2AP1; this effect is seen in both lymphoblastic cell lines (P = 1.18 × 10–5) and in peripheral blood mononuclear cells from subjects with MS (P = 0.01). Thus, we report three new MS susceptibility loci, including a novel inflammatory disease locus that could affect autoreactive cell proliferation.
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影响因子：
3.7
作者：
Comabella M;Craig DW;Camiña-Tato M;Morcillo C;Lopez C;Navarro A;Rio J;BiomarkerMS Study Group;Montalban X;Martin R
通讯作者：
Martin R
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：
5
作者：
Booth, David R.;Heard, Robert N.;Haines, Jonathan
通讯作者：
Haines, Jonathan
影响因子：
30.8
作者：
Lundmark, Frida;Duvefelt, Kristina;Hillert, Jan
通讯作者：
Hillert, Jan
DOI：
10.1016/0197-2456(86)90046-2
发表时间：
1986-09-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
DERSIMONIAN, R;LAIRD, N
通讯作者：
LAIRD, N