CD226 Gly307Ser association with multiple autoimmune diseases.
CD226 Gly307Ser association with multiple autoimmune diseases.
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DOI：
10.1038/gene.2008.82
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发表时间：
2009-01
影响因子：
5
通讯作者：
Todd, J. A.
中科院分区：
文献类型：
--
作者：
Hafler, J. P.;Maier, L. M.;Cooper, J. D.;Plagnol, V.;Hinks, A.;Simmonds, M. J.;Stevens, H. E.;Walker, N. M.;Healy, B.;Howson, J. M. M.;Maisuria, M.;Duley, S.;Coleman, G.;Gough, S. C. L.;Worthington, J.;Kuchroo, V. K.;Wicker, L. S.;Todd, J. A.
全基因组关联（GWA）研究通过识别易感基因和病因途径，深入了解多基因疾病。此外，自身免疫性疾病中共享变异的识别有助于深入了解常见疾病途径。我们之前报道了18号染色体q22区免疫应答基因CD226中的一个非同义单核苷酸多态性（nsSNP）rs763361/Gly307Ser与1型糖尿病（T1D）易感性相关。在此，我们报告了通过外显子重测序以及在1型糖尿病和多发性硬化症（MS）中对18q22区域进行标签单核苷酸多态性（tag SNP）定位来确定致病变异的工作。除了对1型糖尿病（2088例病例和3289例对照）以及自身免疫性甲状腺疾病（AITD）（821例病例和1920例对照）中新获取的样本进行分析，结果强烈支持Ser307与T1D的相关性（P = 3.46×10⁻⁹），并且对AITD仍有潜在证据（P = 0.0345），我们还提供了令人信服的证据证明Gly307Ser与MS相关（P = 4.20×10⁻⁴），以及一些关于另一种自身免疫性疾病类风湿关节炎（RA）的证据（P = 0.017）。CD226第7外显子中rs763361的Ser307等位基因使个体易患T1D、MS，可能还有AITD以及可能还有RA，并且根据标签SNP分析，它可能是致病变异。
Genome-wide association (GWA) studies provide insight into multigenic diseases through the identification of susceptibility genes and etiological pathways. In addition, identification of shared variants among autoimmune disorders provides insight into common disease pathways. We previously reported association of a nonsynonymous single nucleotide polymorphism (nsSNP) rs763361/Gly307Ser in the immune response gene CD226 on chromosome 18q22 with type 1 diabetes (T1D) susceptibility. Here, we report efforts towards identifying the causal variant by exonic resequencing and tag SNP mapping of the 18q22 region in both T1D and multiple sclerosis (MS). In addition to the analysis of newly available samples in T1D (2,088 cases and 3,289 controls) and autoimmune thyroid disease (AITD) (821 cases and 1,920 controls), resulting in strong support for the Ser307 association with T1D (P= 3.46 × 10−9) and continued potential evidence for AITD (P = 0.0345), we provide convincing evidence for association of Gly307Ser with MS (P = 4.20 × 10−4) and some evidence for another autoimmune disease, rheumatoid arthritis (RA) (P = 0.017). The Ser307 allele of rs763361 in exon 7 of CD226 predisposes to T1D, MS, possibly AITD and possibly RA, and based on the tag SNP analysis, could be the causal variant.
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影响因子：
158.5
作者：
Remmers, Elaine F.;Plenge, Robert M.;Gregersen, Peter K.
通讯作者：
Gregersen, Peter K.
影响因子：
9.9
作者：
DOOLITTLE, TH;MYERS, RH;HAUSER, SL
通讯作者：
HAUSER, SL
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：
11.2
作者：
McDonald, WI;Compston, A;Wolinsky, JS
通讯作者：
Wolinsky, JS
影响因子：
3.2
作者：
Brand, Oliver J.;Lowe, Christopher E.;Gough, Stephen C. L.
通讯作者：
Gough, Stephen C. L.