Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians

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• 作者：Wanling Yang¹ ; ²⁹ ; Huayang Tang² ; ²⁹ ; Yan Zhang¹ ; ²⁹ ; Xianfa Tang² ; ²⁹ ; Jing Zhang¹ ; ²⁹ ; Liangdan Sun² ; Jing Yang¹ ; Yong Cui² ; Lu Zhang¹ ; Nattiya Hirankarn³ ; Hui Cheng² ; Hai-Feng Pan⁴ ; Jinping Gao² ; Tsz Leung Lee¹ ; Yujun Sheng² ; Chak Sing Lau⁶ ; Yang Li² ; Tak Mao Chan⁶ ; Xianyong Yin² ; Dingge Ying¹ ; Qianjin Lu⁷ ; Alexander Moon Ho Leung¹⁰ ; Xianbo Zuo² ; Xiang Chen¹¹ ; Kwok Lung Tong¹² ; Fusheng Zhou² ; Qingchun Diao¹³ ; Niko Kei Chiu Tse¹⁴ ; Hongfu Xie¹¹ ; Chi Chiu Mok⁵ ; Fei Hao¹⁵ ; Sik Nin Wong⁹ ; Bingjun Shi¹³ ; Ka Wing Lee⁸ ; Yan Hui¹⁶ ; Marco Hok Kung Ho¹ ; Bo Liang² ; Pamela Pui Wah Lee¹ ; Hongzhou Cui² ; Qing Guo¹⁷ ; Brian Hon-Yin Chung¹ ; Xiongming Pu¹⁸ ; Qiji Liu¹⁹ ; Xiaoguang Zhang² ; Change Zhang² ; Chun Yin Chong¹ ; Hong Fang²⁰ ; Raymond Woon Sing Wong⁶ ; Yonghu Sun² ; Mo Yin Mok⁶ ; Xiang-Pei Li²¹ ; Yingyos Avihingsanon²² ; Zhifang Zhai¹⁵ ; Pornpimol Rianthavorn²³ ; Thavatchai Deekajorndej²³ ; Kanya Suphapeetiporn²³ ; ²⁴ ; Fei Gao⁷ ; Vorasuk Shotelersuk²³ ; ²⁴ ; Xiaojing Kang¹⁸ ; Shirley King Yee Ying¹² ; Lijuan Zhang¹⁶ ; Wilfred Hing Sang Wong¹ ; Dingxian Zhu²⁰ ; Samuel Ka Shun Fung¹² ; Fanqin Zeng¹⁷ ; Wai Ming Lai¹⁴ ; Chun-Ming Wong²⁵ ; Irene Oi Lin Ng²⁵ ; Maria-Mercè ; Garcia-Barceló ; ²⁶ ; Stacey S. Cherny²⁷ ; Nan Shen²⁸ ; Paul Kwong-Hang Tam²⁶ ; Pak Chung Sham²⁷ ; Dong-Qing Ye⁴ ; Sen Yang² ; Xuejun Zhang² ; ^{ayzxj@vip.sina.com} ; Yu Lung Lau¹ ; ^{lauylung@hkucc.hku.hk}
• 刊名：The American Journal of Human Genetics
• 出版年：2013
• 出版时间：10 January, 2013
• 年：2013
• 卷：92
• 期：1
• 页码：41-51
• 全文大小：1144 K

文摘

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases.