单位：[1]Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China中山大学附属第三医院[2]State Key Laboratory of Oncology in South China, Sun Yat-senUniversity Cancer Center, Guangzhou, China[3]Department of Microbiology, National University of Singapore, Singapore[4]Human Genetics, Genome Institute of Singapore,Agency for Science, Technology and Research (A*STAR), Singapore[5]Department of Immunology and Rheumatology,Tongji Hospital,Tongji Medical College,HuazhongUniversity of Science & Technology,Hubei,China华中科技大学同济医学院附属同济医院内科学系风湿免疫内科[6]Department of Rheumatology & Immunology, Beijing Jishuitan Hospital, Beijing, China[7]Department of Rheumatology,Hainan Provincial People’s Hospital, Hainan, China[8]Department of Urology and Rheumatology, The First Affiliated Hospital of Zhengzhou University, Henan, China[9]Department of Rheumatology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, China[10]Rheumatology & Immunology Department, Hospital of IntegratedTraditional Chinese Medicine & Western Medicine of Southern Medical University, Guangzhou, China[11]Department of Rheumatology, Nanfang Hospital, Southern MedicalUniversity, Guangzhou, China[12]Xiangmihu Rheumatology Branch, Fourth People’s Hospital of Shenzhen, Shenzhen Rheumatology Institute of Guangdong Medical College,Shenzhen, China[13]Department of Rheumatology and Immunology, Jinan University Second Clinical Medical College, Shenzhen People’s Hospital, Shenzhen, China深圳市康宁医院深圳市人民医院深圳医学信息中心[14]Department of Immunology and Rheumatology, Union Hospital, Tongji Medical College, Huazhong University of Science & Technology, Hubei, China华中科技大学同济医学院附属协和医院[15]Department ofUrology, Dongguan People’s Hospital, Guangdong, China[16]Department of Rheumatology and Immunology, Second Affiliated Hospital of Guangzhou Medical College,Guangzhou, China[17]Department of Rheumatology and Immunology, The First People′s Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Jiangsu,China[18]Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore[19]Department of Epidemiology and Public Health, YongLoo Lin School of Medicine, National University of Singapore, Singapore[20]Singapore Immunology Network, A*STAR, Singapore[21]Department of Microbiology, NationalUniversity of Singapore, Singapore[22]National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Science andPeking Union Medical College, Tsinghua University, Beijing, China[23]The School of Life Sciences, Anhui Medical University, Hefei, China
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.
基金：
China National
Funds for Distinguished Young Scientists (30325019), The National Natural
Science Foundation of China (30571735), Clinical Subject of the Ministry of Public
Health of China (2007, 2010), the Foundation of Guangdong Province of China
(2005A30801005, 2009B080701086), the Foundation of Guangzhou of China
(2006Z2-E0221), 5010 Subject of Sun Yat-sen University (2009–2010) and the
Agency of Science, Technology and Research (A*STAR) of Singapore.
第一作者单位：[1]Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
共同第一作者：
通讯作者：
通讯机构：[4]Human Genetics, Genome Institute of Singapore,Agency for Science, Technology and Research (A*STAR), Singapore[23]The School of Life Sciences, Anhui Medical University, Hefei, China
推荐引用方式(GB/T 7714)：
Zhiming Lin,Jin-Xin Bei,Meixin Shen,et al.A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis[J].NATURE GENETICS.2012,44(1):73-U104.doi:10.1038/ng.1005.
APA：
Zhiming Lin,Jin-Xin Bei,Meixin Shen,Qiuxia Li,Zetao Liao...&Jieruo Gu.(2012).A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis.NATURE GENETICS,44,(1)
MLA：
Zhiming Lin,et al."A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis".NATURE GENETICS 44..1(2012):73-U104
生物