Novel risk loci for rheumatoid arthritis in han chinese and congruence with risk variants in europeans

Jiang, Lei, Yin, Jian, Ye, Lingying, Yang, Jian, Hemani, Gibran, Liu, Ai-Jun, Zou, Hejian, He, Dongyi, Sun, Lingyun, Zeng, Xiaofeng, Li, Zhanguo, Zheng Yi, Lin, Yiping, Liu, Yi, Fang, Yongfei, Xu, Jianhua, Li, Yinong, Dai, Shengming, Guan, Jianlong, Jiang, Lindi, Wei, Qianghua, Wang, Yi, Li, Yang, Huang, Cibo, Zuo, Xiaoxia, Liu, Yu, Wu, Xin, Zhang, Libin, Zhou, Ling, Zhang, Qing, Li, Ting, Chen, Ling, Xu, Zhen, Yang, Xiaoping, Qian, Feng, Xie, Weilin, Liu Wei, Guo, Qian, Huang, Weilin, Zhao, Jing, Li, Mengmeng, Jin, Yanhua, Gao, Jie, Lv, Yeng, Wang, Yiwen, Lin, Li, Guo, Aihua, Danoy, Patrick, Willner, Dana, Cremin, Catherine, Hadler, Johanna, Zhang, Fengchun, Zhao, Yan, Li, Mengtao, Yue, Tao, Fan, Xiaolei, Guo, Jianping, Mu, Rong, Li, Jingyi, Wu, Chao, Zeng, Ming, Wang, Jiucun, Li, Shilin, Jin, Li, Wang, Binbin, Wang, Jing, Ma, Xu, Sun, Liangdan, Zhang, Xuejun, Brown, Matthew A., Visscher, Peter M., Su, Ding-feng and Xu, Huji (2014) Novel risk loci for rheumatoid arthritis in han chinese and congruence with risk variants in europeans. Arthritis and Rheumatology, 66 5: 1121-1132. doi:10.1002/art.38353


Author Jiang, Lei
Yin, Jian
Ye, Lingying
Yang, Jian
Hemani, Gibran
Liu, Ai-Jun
Zou, Hejian
He, Dongyi
Sun, Lingyun
Zeng, Xiaofeng
Li, Zhanguo
Zheng Yi
Lin, Yiping
Liu, Yi
Fang, Yongfei
Xu, Jianhua
Li, Yinong
Dai, Shengming
Guan, Jianlong
Jiang, Lindi
Wei, Qianghua
Wang, Yi
Li, Yang
Huang, Cibo
Zuo, Xiaoxia
Liu, Yu
Wu, Xin
Zhang, Libin
Zhou, Ling
Zhang, Qing
Li, Ting
Chen, Ling
Xu, Zhen
Yang, Xiaoping
Qian, Feng
Xie, Weilin
Liu Wei
Guo, Qian
Huang, Weilin
Zhao, Jing
Li, Mengmeng
Jin, Yanhua
Gao, Jie
Lv, Yeng
Wang, Yiwen
Lin, Li
Guo, Aihua
Danoy, Patrick
Willner, Dana
Cremin, Catherine
Hadler, Johanna
Zhang, Fengchun
Zhao, Yan
Li, Mengtao
Yue, Tao
Fan, Xiaolei
Guo, Jianping
Mu, Rong
Li, Jingyi
Wu, Chao
Zeng, Ming
Wang, Jiucun
Li, Shilin
Jin, Li
Wang, Binbin
Wang, Jing
Ma, Xu
Sun, Liangdan
Zhang, Xuejun
Brown, Matthew A.
Visscher, Peter M.
Su, Ding-feng
Xu, Huji
Title Novel risk loci for rheumatoid arthritis in han chinese and congruence with risk variants in europeans
Journal name Arthritis and Rheumatology   Check publisher's open access policy
ISSN 2326-5205
2326-5191
Publication date 2014
Sub-type Article (original research)
DOI 10.1002/art.38353
Open Access Status
Volume 66
Issue 5
Start page 1121
End page 1132
Total pages 12
Place of publication Hoboken, NJ, United States
Publisher John Wiley and Sons
Collection year 2015
Language eng
Formatted abstract
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 × 10 -21), and rs12379034, located in the coding region of CDK5RAP2 (OR 1.49, P = 1.1 × 10-16), as well as a variant at the known CCR6 locus, rs1854853 (OR 0.71, P = 6.5 × 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 × 10-18), and such an interaction was also observed for rs7748270 at the MHC locus (P = 5.9 × 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
 
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