Novel Risk Loci for Rheumatoid Arthritis in Han Chinese and Congruence With Risk Variants in Europeans

被引：81

作者：

Jiang, Lei ^{[1
,2
]}

Yin, Jian ^{[1
,2
]}

Ye, Lingying ^{[1
,2
]}

Yang, Jian ^{[3
,4
]}

Hemani, Gibran ^{[3
,4
]}

Liu, Ai-Jun ^{[5
]}

Zou, Hejian ^{[6
,7
]}

He, Dongyi ^{[8
]}

Sun, Lingyun ^{[9
]}

Zeng, Xiaofeng ^{[10
,11
]}

Li, Zhanguo ^{[12
,13
]}

Zheng, Yi ^{[14
,15
]}

Lin, Yiping ^{[16
]}

Liu, Yi ^{[17
,18
]}

Fang, Yongfei ^{[19
,20
]}

Xu, Jianhua ^{[21
]}

Li, Yinong ^{[22
,23
]}

Dai, Shengming ^{[24
,25
]}

Guan, Jianlong ^{[26
,27
]}

Jiang, Lindi ^{[27
,28
]}

Wei, Qianghua ^{[29
]}

Wang, Yi ^{[30
]}

Li, Yang ^{[31
]}

Huang, Cibo ^{[32
]}

Zuo, Xiaoxia ^{[33
,34
]}

Liu, Yu ^{[1
,2
]}

Wu, Xin ^{[1
,2
]}

Zhang, Libin ^{[1
,2
]}

Zhou, Ling ^{[1
,2
]}

Zhang, Qing ^{[1
,2
]}

Li, Ting ^{[1
,2
]}

Chen, Ling ^{[1
,2
]}

Xu, Zhen ^{[1
,2
]}

Yang, Xiaoping ^{[1
,2
]}

Qian, Feng ^{[1
,2
]}

Xie, Weilin ^{[1
,2
]}

Liu, Wei ^{[35
,36
,37
]}

Guo, Qian ^{[1
,2
]}

Huang, Shaolan ^{[1
,2
]}

Zhao, Jing ^{[1
,2
]}

Li, Mengmeng ^{[1
,2
]}

Jin, Yanhua ^{[1
,2
]}

Gao, Jie ^{[1
,2
]}

Lv, Ying ^{[1
,2
]}

Wang, Yiwen ^{[1
,2
]}

Lin, Li ^{[1
,2
]}

Guo, Aihua ^{[1
,2
]}

Danoy, Patrick ^{[3
,4
]}

Willner, Dana ^{[3
,4
]}

Cremin, Catherine ^{[3
,4
]}

机构：

[1] Shanghai Changzheng Hosp, Shanghai, Peoples R China

[2] Second Mil Med Univ, Shanghai, Peoples R China

[3] Princess Alexandra Hosp, Brisbane, Qld 4102, Australia

[4] Univ Queensland, Brisbane, Qld, Australia

[5] Second Mil Med Univ, Shanghai, Peoples R China

[6] Huashan Hosp, Shanghai, Peoples R China

[7] Fudan Univ, Shanghai 200433, Peoples R China

[8] Guanghua Hosp, Shanghai, Peoples R China

[9] Nanjing Med Univ, Nanjing, Jiangsu, Peoples R China

[10] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Beijing 100730, Peoples R China

[11] Peking Union Med Coll, Beijing 100021, Peoples R China

[12] Peoples Hosp, Beijing, Peoples R China

[13] Beijing Univ, Beijing 100871, Peoples R China

[14] Beijing Chaoyang Hosp, Beijing, Peoples R China

[15] Capital Med Univ, Beijing, Peoples R China

[16] Peoples Liberat Army, Hosp 202, Shenyang, Peoples R China

[17] West China Hosp, Chengdu, Peoples R China

[18] Sichuan Univ, Chengdu 610064, Peoples R China

[19] Southwest Hosp, Chongqing, Peoples R China

[20] Third Mil Med Univ, Chongqing, Peoples R China

[21] Anhui Med Univ, Affiliated Hosp 1, Hefei, Peoples R China

[22] Peoples Hosp Fujian Prov, Fuzhou, Peoples R China

[23] Fujian Univ Tradit Chinese Med, Fuzhou, Peoples R China

[24] Shanghai Changhai Hosp, Shanghai, Peoples R China

[25] Second Mil Med Univ, Shanghai, Peoples R China

[26] Huadong Hosp, Shanghai, Peoples R China

[27] Fudan Univ, Shanghai 200433, Peoples R China

[28] Zhongshan Hosp, Shanghai, Peoples R China

[29] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 1, Shanghai 200030, Peoples R China

[30] Lanzhou Univ, Hosp 2, Lanzhou 730000, Peoples R China

[31] Harbin Med Univ, Affiliated Hosp 2, Harbin, Peoples R China

[32] Beijing Hosp, Beijing, Peoples R China

[33] Xiangya Hosp, Changsha, Hunan, Peoples R China

[34] Cent S Univ, Changsha, Hunan, Peoples R China

[35] Shanghai Changzheng Hosp, Shanghai 200003, Peoples R China

[36] Second Mil Med Univ, Shanghai 200433, Peoples R China

[37] Fuzhou Gen Hosp, Hosp 442, Ningde, Peoples R China

[38] Third Mil Med Univ, Chongqing, Peoples R China

[39] Natl Inst Food & Drug Control, Beijing, Peoples R China

[40] Fudan Univ, Shanghai 200433, Peoples R China

[41] Natl Res Inst Family Planning, Beijing, Peoples R China

[42] Natl Res Inst Family Planning, Beijing, Peoples R China

[43] Capital Med Univ, Beijing, Peoples R China

[44] Anhui Med Univ, Hefei, Anhui, Peoples R China

来源：

ARTHRITIS & RHEUMATOLOGY | 2014年 / 66卷 / 05期

基金：

英国医学研究理事会; 中国国家自然科学基金;

关键词：

GENOME-WIDE ASSOCIATION; ANKYLOSING-SPONDYLITIS; TH17; CELLS; POPULATION; SUSCEPTIBILITY; EPIDEMIOLOGY; DISEASES; DENSITY; SCAN; MAP;

D O I：

10.1002/art.38353

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective. To investigate differences in genetic risk factors for rheumatoid arthritis (RA) in Han Chinese as compared with Europeans. Methods. A genome-wide association study was conducted in China with 952 patients and 943 controls, and 32 variants were followed up in 2,132 patients and 2,553 controls. A transpopulation meta-analysis with results from a large European RA study was also performed to compare the genetic architecture across the 2 ethnic remote populations. Results. Three non-major histocompatibility complex (non-MHC) loci were identified at the genome-wide significance level, the effect sizes of which were larger in anti-citrullinated protein antibody (ACPA)-positive patients than in ACPA-negative patients. These included 2 novel variants, rs12617656, located in an intron of DPP4 (odds ratio [OR] 1.56, P = 1.6 x 10(-21)), and rs12379034, located in the coding region of CDK5RAP2 (OR 1.49, P = 1.1 x 10(-16)), as well as a variant at the known CCR6 locus, rs1854853 (OR 0.71, P = 6.5 x 10(-15)). The analysis of ACPA-positive patients versus ACPA-negative patients revealed that rs12617656 at the DPP4 locus showed a strong interaction effect with ACPAs (P = 5.3 x 10(-18)), and such an interaction was also observed for rs7748270 at the MHC locus (P = 5.9 x 10(-8)). The transpopulation meta-analysis showed genome-wide overlap and enrichment in association signals across the 2 populations, as confirmed by prediction analysis. Conclusion. This study has expanded the list of alleles that confer risk of RA, provided new insight into the pathogenesis of RA, and added empirical evidence to the emerging polygenic nature of complex trait variation driven by common genetic variants.

引用

页码：1121 / 1132

页数：12

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