Abstract
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.
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Acknowledgements
We thank all participants recruited for this study. We also thank Y. Xie, X. Guo, Q. Li, L. Zhao, S. Zhang, Z. Huang and Z. Guo for providing suggestions and for their help in the recruitment of subjects. This work was funded by 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.
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J.G. and J. Liu conceived of the study and obtained financial support. J.G., J. Liu and J.-X.B. designed the study. Z. Lin, Z. Liao, Y.Z., Q. Lv, S.C., M.Y., Z.H., M.X., X.W., Y. Wei, L.L., C.L., T.L., J.H., Y.P., O.J., Y. Wu, J.W., Z.G., P.H., S.H., Husheng Wu, H.S., F.Z., S.L., G.G., Z. Liu, Y.L., C.X., J. Li, Z.Y., W.H., D.L., L.S., A.H., Henglian Wu, Y.T., X.P. and B.Y. coordinated recruitment and obtained biological samples. Z. Lin, Q. Li and Q.W. undertook sample preparation and storage. M.S. and E.C.R. were involved in HLA genotyping. E.S.T. and Y.-X.Z. provided genotypes. J.-X.B. conducted the statistical analyses with help from H.-Q.L., Z. Lin, Y.-M.G., Y.S. and J. Liu. J.-X.B. drafted the manuscript with contributions from J. Liu, Z. Lin, Y.Z., E.C.R. and J.G.
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Lin, Z., Bei, JX., Shen, M. et al. A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis. Nat Genet 44, 73–77 (2012). https://doi.org/10.1038/ng.1005
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DOI: https://doi.org/10.1038/ng.1005
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