A genome-wide association study identifies two new risk loci for Graves' disease

被引：212

作者：

Chu, Xun ^{[1
,2
]}

Pan, Chun-Ming ^{[1
,3
]}

Zhao, Shuang-Xia ^{[1
,3
]}

Liang, Jun ^{[4
]}

Gao, Guan-Qi ^{[5
]}

Zhang, Xiao-Mei ^{[6
]}

Yuan, Guo-Yue ^{[7
]}

Li, Chang-Gui ^{[8
,9
]}

Xue, Li-Qiong ^{[1
]}

Shen, Min ^{[2
]}

Liu, Wei ^{[1
]}

Xie, Fang ^{[1
,2
]}

Yang, Shao-Ying ^{[1
]}

Wang, Hai-Feng ^{[2
]}

Shi, Jing-Yi ^{[1
]}

Sun, Wei-Wei ^{[2
]}

Du, Wen-Hua ^{[5
]}

Zuo, Chun-Lin ^{[1
]}

Shi, Jin-Xiu ^{[1
,2
]}

Liu, Bing-Li ^{[1
]}

Guo, Cui-Cui ^{[1
]}

Zhan, Ming ^{[1
]}

Gu, Zhao-Hui ^{[1
]}

Zhang, Xiao-Na ^{[1
]}

Sun, Fei ^{[1
]}

Wang, Zhi-Quan ^{[1
]}

Song, Zhi-Yi ^{[1
]}

Zou, Cai-Yan ^{[4
]}

Sun, Wei-Hua ^{[6
]}

Guo, Ting ^{[1
,3
]}

Cao, Huang-Ming ^{[1
]}

Ma, Jun-Hua ^{[1
]}

Han, Bing ^{[1
]}

Li, Ping ^{[1
,3
]}

Jiang, He ^{[1
]}

Huang, Qiu-Hua ^{[1
]}

Liang, Liming ^{[10
]}

Liu, Li-Bin ^{[11
]}

Chen, Gang ^{[12
]}

Su, Qing ^{[13
]}

Peng, Yong-De ^{[14
]}

Zhao, Jia-Jun ^{[15
]}

Ning, Guang ^{[3
]}

Chen, Zhu ^{[1
]}

Chen, Jia-Lun ^{[1
,3
]}

Chen, Sai-Juan

Huang, Wei ^{[2
]}

Song, Huai-Dong ^{[3
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, State Key Lab Med Genom, Ruijin Hosp, Shanghai 200030, Peoples R China

[2] Shanghai Minist Sci & Technol MOST, Dept Genet, Key Lab Hlth & Dis Genom, Chinese Natl Human Genome Ctr, Shanghai, Peoples R China

[3] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Shanghai Inst Endocrinol & Metab,Dept Endocrinol, Shanghai 200030, Peoples R China

[4] Xuzhou Med Coll, Dept Endocrinol, Cent Hosp Xuzhou, Xuzhou, Jiangsu Prov, Peoples R China

[5] Peoples Hosp Linyi, Dept Endocrinol, Linyi, Shandong, Peoples R China

[6] Bengbu Med Coll, Dept Endocrinol, Hosp 1, Bengbu, Anhui, Peoples R China

[7] Jiangsu Univ, Dept Endocrinol, Zhenjiang, Jiangsu Prov, Peoples R China

[8] Qingdao Univ, Dept Endocrinol, Med Sch Hosp, Qingdao 266071, Shandong, Peoples R China

[9] Qingdao Univ, Gout Lab, Med Sch Hosp, Qingdao 266071, Shandong, Peoples R China

[10] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02115 USA

[11] Fujian Med Univ, Xiehe Hosp, Dept Endocrinol, Fuzhou, Fujian Province, Peoples R China

[12] Fujian Prov Hosp, Dept Endocrinol, Fuzhou, Fujian Province, Peoples R China

[13] Shanghai Jiao Tong Univ, Sch Med, Dept Endocrinol, Xin Hua Hosp, Shanghai 200030, Peoples R China

[14] Shanghai Jiao Tong Univ, Dept Endocrinol, Peoples Hosp 1, Shanghai 200030, Peoples R China

[15] Shandong Univ, Dept Endocrinol, Shandong Prov Hosp, Jinan 250100, Shandong, Peoples R China

来源：

NATURE GENETICS | 2011年 / 43卷 / 09期

基金：

中国国家自然科学基金;

关键词：

THYROTROPIN RECEPTOR ANTIBODIES; RHEUMATOID-ARTHRITIS; SUSCEPTIBILITY LOCI; GENE; SNPS; VARIANTS; POPULATION; VITILIGO; OMEGA-1; CTLA4;

D O I：

10.1038/ng.898

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Graves' disease is a common autoimmune disorder characterized by thyroid stimulating hormone receptor autoantibodies (TRAb) and hyperthyroidism. To investigate the genetic architecture of Graves' disease, we conducted a genome-wide association study in 1,536 individuals with Graves' disease (cases) and 1,516 controls. We further evaluated a group of associated SNPs in a second set of 3,994 cases and 3,510 controls. We confirmed four previously reported loci (in the major histocompatibility complex, TSHR, CTLA4 and FCRL3) and identified two new susceptibility loci (the RNASET2-FGFR1OP-CCR6 region at 6q27 (P-combined = 6.85 x 10(-10) for rs9355610) and an intergenic region at 4p14 (P-combined = 1.08 x 10(-13) for rs6832151)). These newly associated SNPs were correlated with the expression levels of RNASET2 at 6q27, of CHRNA9 and of a previously uncharacterized gene at 4p14, respectively. Moreover, we identified strong associations of TSHR and major histocompatibility complex class II variants with persistently TRAb-positive Graves' disease.

引用

页码：897 / U114

页数：6

共 32 条

[1]

Acquati F, 2005, INT J ONCOL, V26, P1159

[2] ProbABEL package for genome-wide association analysis of imputed data [J].

Aulchenko, Yurii S. ;

Struchalin, Maksim V. ;

van Duijn, Cornelia M. .

BMC BIOINFORMATICS, 2010, 11

[3] Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease [J].

Barrett, Jeffrey C. ;

Hansoul, Sarah ;

Nicolae, Dan L. ;

Cho, Judy H. ;

Duerr, Richard H. ;

Rioux, John D. ;

Brant, Steven R. ;

Silverberg, Mark S. ;

Taylor, Kent D. ;

Barmada, M. Michael ;

Bitton, Alain ;

Dassopoulos, Themistocles ;

Datta, Lisa Wu ;

Green, Todd ;

Griffiths, Anne M. ;

Kistner, Emily O. ;

Murtha, Michael T. ;

Regueiro, Miguel D. ;

Rotter, Jerome I. ;

Schumm, L. Philip ;

Steinhart, A. Hillary ;

Targan, Stephan R. ;

Xavier, Ramnik J. ;

Libioulle, Cecile ;

Sandor, Cynthia ;

Lathrop, Mark ;

Belaiche, Jacques ;

Dewit, Olivier ;

Gut, Ivo ;

Heath, Simon ;

Laukens, Debby ;

Mni, Myriam ;

Rutgeerts, Paul ;

Van Gossum, Andre ;

Zelenika, Diana ;

Franchimont, Denis ;

Hugot, Jean-Pierre ;

de Vos, Martine ;

Vermeire, Severine ;

Louis, Edouard ;

Cardon, Lon R. ;

Anderson, Carl A. ;

Drummond, Hazel ;

Nimmo, Elaine ;

Ahmad, Tariq ;

Prescott, Natalie J. ;

Onnie, Clive M. ;

Fisher, Sheila A. ;

Marchini, Jonathan ;

Ghori, Jilur .

NATURE GENETICS, 2008, 40 (08) :955-962

[4] Association of the thyroid stimulating hormone receptor gene (TSHR) with Graves' disease [J].

Brand, Oliver J. ;

Barrett, Jeffrey C. ;

Simmonds, Matthew J. ;

Newby, Paul R. ;

McCabe, Christopher J. ;

Bruce, Christopher K. ;

Kysela, Boris ;

Carr-Smith, Jackie D. ;

Brix, Thomas ;

Hunt, Penny J. ;

Wiersinga, Wilmar M. ;

Hegedus, Laszlo ;

Connell, John ;

Wass, John A. H. ;

Franklyn, Jayne A. ;

Weetman, Anthony P. ;

Heward, Joanne M. ;

Gough, Stephen C. L. .

HUMAN MOLECULAR GENETICS, 2009, 18 (09) :1704-1713

[5]

Breslow N E, 1980, IARC Sci Publ, P5

[6] Prognostic value of thyrotropin receptor antibodies (TRAb) in Graves' disease: A 120 months prospective study [J].

Cappelli, Carlo ;

Gandossi, Elena ;

Castellano, Maurizio ;

Pizzocaro, Claudio ;

Agosti, Barbara ;

Delbarba, Andrea ;

Pirola, Ilenia ;

De Martino, Elvira ;

Rosei, Enrico Agabiti .

ENDOCRINE JOURNAL, 2007, 54 (05) :713-720

[7] Serum thyrotropin receptor antibodies concentrations in patients with Graves' disease before, at the end of methimazole treatment, and after drug withdrawal: Evidence that the activity of thyrotropin receptor antibody and/or thyroid response modify during the observation period [J].

Carella, C ;

Mazziotti, G ;

Sorvillo, F ;

Piscopo, M ;

Cioffi, M ;

Pilla, P ;

Nersita, R ;

Iorio, S ;

Amato, G ;

Braverman, LE ;

Roti, E .

THYROID, 2006, 16 (03) :295-302

[8] Is FCRL3 a new general autoimmunity gene? [J].

Chistiakov, Dimitry A. ;

Chistiakov, Alexander P. .

HUMAN IMMUNOLOGY, 2007, 68 (05) :375-383

[9] A genome-wide association study of global gene expression [J].

Dixon, Anna L. ;

Liang, Liming ;

Moffatt, Miriam F. ;

Chen, Wei ;

Heath, Simon ;

Wong, Kenny C. C. ;

Taylor, Jenny ;

Burnett, Edward ;

Gut, Ivo ;

Farrall, Martin ;

Lathrop, G. Mark ;

Abecasis, Goncalo R. ;

Cookson, William O. C. .

NATURE GENETICS, 2007, 39 (10) :1202-1207

[10] Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses [J].

Everts, Bart ;

Perona-Wright, Georgia ;

Smits, Hermelijn H. ;

Hokke, Cornelis H. ;

van der Ham, Alwin J. ;

Fitzsimmons, Colin M. ;

Doenhoff, Michael J. ;

van der Bosch, Juergen ;

Mohrs, Katja ;

Haas, Helmut ;

Mohrs, Markus ;

Yazdanbakhsh, Maria ;

Schramm, Gabriele .

JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (08) :1673-1680

← 1 2 3 4 →