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

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

Nature genetics (2011-12-06)

Zhiming Lin, Jin-Xin Bei, Meixin Shen, Qiuxia Li, Zetao Liao, Yanli Zhang, Qing Lv, Qiujing Wei, Hui-Qi Low, Yun-Miao Guo, Shuangyan Cao, Mingcan Yang, Zaiying Hu, Manlong Xu, Xinwei Wang, Yanlin Wei, Li Li, Chao Li, Tianwang Li, Jianlin Huang, Yunfeng Pan, Ou Jin, Yuqiong Wu, Jing Wu, Zishi Guo, Peigen He, Shaoxian Hu, Husheng Wu, Hui Song, Feng Zhan, Shengyun Liu, Guanmin Gao, Zhangsuo Liu, Yinong Li, Changhong Xiao, Juan Li, Zhizhong Ye, Weizhen He, Dongzhou Liu, Lingxun Shen, Anbin Huang, Henglian Wu, Yi Tao, Xieping Pan, Buyun Yu, E Shyong Tai, Yi-Xin Zeng, Ee Chee Ren, Yan Shen, Jianjun Liu, Jieruo Gu

PMID22138694

摘要

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 × 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 × 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 × 10(-324)) and at 2p15 (rs10865331; P = 1.98 × 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.