TY - JOUR T1 - Analysis of 47 non-MHC Ankylosing Spondylitis Susceptibility Loci Reveals Shared Associated Variants across Caucasians and Han Chinese JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.190184 SP - jrheum.190184 AU - Xuqi Zheng AU - Qiuxia Li AU - Xiaomin Li AU - Yanli Zhang AU - Xinyu Wu AU - Qiujing Wei AU - Shuangyan Cao AU - Mingcan Yang AU - Zhiming Lin AU - Zetao Liao AU - Jun Qi AU - Qing Lv AU - Ling Wang AU - Yi Li AU - Astrid Irwanto AU - Ching-Yu Cheng AU - Xiaoran Chai AU - Chiea Chuen Khor AU - Chew-Kiat Heng AU - Woon-Puay Koh AU - Jian-Min Yuan AU - Jinxin Bei AU - Furen Zhang AU - Xuejun Zhang AU - Yixin Zeng AU - Yan Shen AU - Jianjun Liu AU - Jieruo Gu Y1 - 2019/09/15 UR - http://www.jrheum.org/content/early/2019/09/11/jrheum.190184.abstract N2 - Objective We aimed to present a systematic evaluation of 47 non Major Histocompatibility Complex (MHC) Ankylosing Spondylitis (AS) susceptibility loci which have been initially discovered through Caucasian Genome-wide association studies (GWASs) in Han Chinese. Methods Totally 10,743 samples representing north and south Chinese in four datasets were obtained. After data quality control and imputation, meta-analysis results of 94,621 variants within 47 loci were extracted. Four ERAP1 single-nucleotide polymorphisms (SNPs) and HLA-B27 tag SNP rs13202464 were used for interaction analysis. Population-attributable risk percentages (PARPs) of AS-associated variants were compared. Functional annotation of AS-associated variants were conducted using HaploReg, RegulomeDB and rVarBase Database. Results We revealed 16 AS-associated variants with nominal evidence in Han Chinese, including rs10865331 (P=6.30×10-10), rs10050860 (P=4.09×10-5) and rs8070463 (P=1.03×10-4). Potential susceptible SNPs within these 47 loci were also identified, such as rs13024541 (2p15), rs17401719 (5q15) and rs62074054 (17q21). Epistatic ineractions between three ERAP1 SNPs (rs17401719, rs30187 and rs10050860) and HLA-B27 were confirmed. Among the 16 AS-associated variants, rs30187 showed weaker risk effect while rs10050860 and rs12504282 seemed to attribute more risk in Han Chinese than Caucasians. Further genomic annotation pinpointed 35 candidate functional SNPs, especially in 2p15, ERAP1 and NPEPPS-TBKBP1 region. Conclusion Our results provided a detailed spectrum of all the reported non-MHC AS susceptibility loci in Han Chinese, which comprehensively exhibited the ethnic heterogeneity of AS susceptibility and highlighted that 2p15, ERAP1 and NPEPPS-TBKBP1 region may play a critical role in AS pathogenesis across diverse populations. ER -