학술논문
Meta-analysis of GWAS on two Chinese populations followed by replication identifies novel genetic variants on the X chromosome associated with systemic lupus erythematosus
Document Type
Academic Journal
Author
Zhang, Yan; Zhang, Jing; Yang, Jing; Wang, Yongfei; Zhang, Lu; Zuo, Xianbo; Sun, Liangdan; Pan, Hai-Feng; Hirankarn, Nattiya; Wang, Tingyou; Chen, Ruoyan; Ying, Dingge; Zeng, Shuai; Shen, Jiangshan Jane; Lee, Tsz Leung; Lau, Chak Sing; Chan, Tak Mao; Leung, Alexander Moon Ho; Mok, Chi Chiu; Wong, Sik Nin; Lee, Ka Wing; Ho, Marco Hok Kung; Lee, Pamela Pui Wah; Chung, Brian Hon-Yin; Chong, Chun Yin; Wong, Raymond Woon Sing; Mok, Mo Yin; Wong, Wilfred Hing Sang; Tong, Kwok Lung; Tse, Niko Kei Chiu; Li, Xiang-Pei; Avihingsanon, Yingyos; Rianthavorn, Pornpimol; Deekajorndej, Thavatchai; Suphapeetiporn, Kanya; Shotelersuk, Vorasuk; Ying, Shirley King Yee; Fung, Samuel Ka Shun; Lai, Wai Ming; Wong, Chun-Ming; Ng, Irene Oi Lin; Garcia-Barcelo, Maria-Merce; Cherny, Stacey S.; Tam, Paul Kwong-Hang; Sham, Pak Chung; Yang, Sen; Ye, Dong Qing; Cui, Yong; Zhang, Xue-Jun; Lau, Yu Lung; Yang, Wanling
Source
Human Molecular Genetics. Jan 01, 2015 24(1):274-284
Subject
Language
English
ISSN
0964-6906
Abstract
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that affects mainly females. What role the X chromosome plays in the disease has always been an intriguing question. In this study, we examined the genetic variants on the X chromosome through meta-analysis of two genome-wide association studies (GWAS) on SLE on Chinese Han populations. Prominent association signals from the meta-analysis were replicated in 4 additional Asian cohorts, with a total of 5373 cases and 9166 matched controls. We identified a novel variant in PRPS2 on Xp22.3 as associated with SLE with genome-wide significance (rs7062536, OR = 0.84, P = 1.00E−08). Association of the L1CAM-MECP2 region with SLE was reported previously. In this study, we identified independent contributors in this region in NAA10 (rs2071128, OR = 0.81, P = 2.19E−13) and TMEM187 (rs17422, OR = 0.75, P = 1.47E−15), in addition to replicating the association from IRAK1-MECP2 region (rs1059702, OR = 0.71, P = 2.40E−18) in Asian cohorts. The X-linked susceptibility variants showed higher effect size in males than that in females, similar to results from a genome-wide survey of associated SNPs on the autosomes. These results suggest that susceptibility genes identified on the X chromosome, while contributing to disease predisposition, might not contribute significantly to the female predominance of this prototype autoimmune disease.