Title |
Novel Risk Loci for Rheumatoid Arthritis in Han Chinese and Congruence With Risk Variants in Europeans
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Published in |
Arthritis & Rheumatology, April 2014
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DOI | 10.1002/art.38353 |
Pubmed ID | |
Authors |
Lei Jiang, Jian Yin, Lingying Ye, Jian Yang, Gibran Hemani, Ai‐jun Liu, Hejian Zou, Dongyi He, Lingyun Sun, Xiaofeng Zeng, Zhanguo Li, Yi Zheng, Yiping Lin, Yi Liu, Yongfei Fang, Jianhua Xu, Yinong Li, Shengming Dai, Jianlong Guan, Lindi Jiang, Qianghua Wei, Yi Wang, Yang Li, Cibo Huang, Xiaoxia Zuo, Yu Liu, Xin Wu, Libin Zhang, Ling Zhou, Qing Zhang, Ting Li, Ling Chen, Zhen Xu, Xiaoping Yang, Feng Qian, Weilin Xie, Wei Liu, Qian Guo, Shaolan Huang, Jing Zhao, Mengmeng Li, Yanhua Jin, Jie Gao, Ying Lv, Yiwen Wang, Li Lin, Aihua Guo, Patrick Danoy, Dana Willner, Catherine Cremin, Johanna Hadler, Fengchun Zhang, Yan Zhao, Mengtao Li, Tao Yue, Xiaolei Fan, Jianping Guo, Rong Mu, Jingyi Li, Chao Wu, Ming Zeng, Jiucun Wang, Shilin Li, Li Jin, Binbin Wang, Jing Wang, Xu Ma, Liangdan Sun, Xuejun Zhang, Matthew A. Brown, Peter M. Visscher, Ding‐feng Su, Huji Xu |
Abstract |
Aims: This study was designed to investigate differences in genetic risk factors for rheumatoid arthritis (RA) in Han Chinese compared with Europeans. Methods: A genome-wide association study was conducted in China with 952 cases and 943 controls and 32 variants were followed up in 2132 cases and 2553 controls. A trans-population meta-analysis with results from a large European RA study was also performed to compare the genetic architecture across the two ethnic remote populations Results: Three non-MHC loci were identified at the genome-wide significance level, the effect sizes of which were larger in anti-citrullinated peptide antibody (ACPA) positive cases than those in ACPA-negative cases. These include two 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 cases vs. ACPA-negative cases revealed that rs12617656 at the DDP4 locus showed a strong interaction effect with ACPA (P = 5.3 × 10(-18) ) and such an interaction was also observed at the MHC locus (rs7748270, P = 5.9 × 10(-8) ). The trans-population meta-analysis showed genome-wide overlap and enrichment in association signals across the two populations, confirmed by prediction analysis. Conclusions: This study has expanded the risk alleles list 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. © 2013 American College of Rheumatology. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 2% |
Netherlands | 1 | 2% |
Unknown | 55 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 12 | 21% |
Student > Ph. D. Student | 10 | 18% |
Student > Master | 9 | 16% |
Student > Bachelor | 5 | 9% |
Other | 5 | 9% |
Other | 9 | 16% |
Unknown | 7 | 12% |
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Agricultural and Biological Sciences | 14 | 25% |
Medicine and Dentistry | 13 | 23% |
Biochemistry, Genetics and Molecular Biology | 6 | 11% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 4% |
Immunology and Microbiology | 2 | 4% |
Other | 8 | 14% |
Unknown | 12 | 21% |