A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis

作者：Lin, Zhiming; Bei, Jin-Xin; Shen, Meixin; Li, Qiuxia; Liao, Zetao; Zhang, Yanli; Lv, Qing; Wei, Qiujing; Low, Hui-Qi; Guo, Yun-Miao; Cao, Shuangyan; Yang, Mingcan; Hu, Zaiying; Xu, Manlong; Wang, Xinwei; Wei, Yanlin; Li, Li; Li, Chao; Li, Tianwang; Huang, Jianlin; Pan, Yunfeng; Jin, Ou; Wu, Yuqiong; Wu, Jing; Guo, Zishi; He, Peigen; Hu, Shaoxian; Wu, Husheng; Song, Hui; Zhan, Feng; Liu, Shengyun; Gao, Guanmin; Liu, Zhangsuo; Li, Yinong; Xiao, Changhong; Li, Juan; Ye, Zhizhong; He, Weizhen

来源：Nature Genetics, 2012, 44(1): 73-U104.

DOI：10.1038/ng.1005

• HLA-B27
• POPULATION
• MATURATION
• VARIANTS
• SUBTYPES
• PROTEIN
• ERAP1

To identify susceptibility loci for ankylosing spondylitis, we performed a two-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing spondylitis and 4,231 controls; in the validation stage, we analyzed 30 suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls. We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569; P = 8.77 x 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 x 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 x 10(-324)) and at 2p15 (rs10865331; P = 1.98 x 10(-8)). We show that rs13202464 within the MHC region mainly represents the risk effect of HLA-B*27 variants (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly discovered loci implicate genes related to bone formation and cartilage development, suggesting their potential involvement in the etiology of ankylosing spondylitis.

• 出版日期2012-1
• 单位广州医科大学; 安徽医科大学; 郑州大学; 广东医科大学; 华中科技大学; 北京协和医学院; 清华大学; 中国医学科学院北京协和医院; 海南省人民医院; 苏州大学; 中国人民解放军南京军区福州总医院; 南方医科大学; 华南肿瘤学国家重点实验室; 北京积水潭医院; 暨南大学; 中山大学