Title |
Meta-analysis of two Chinese populations identifies an autoimmune disease risk allele in 22q11.21 as associated with systemic lupus erythematosus
|
---|---|
Published in |
Arthritis Research & Therapy, March 2015
|
DOI | 10.1186/s13075-015-0577-6 |
Pubmed ID | |
Authors |
Yan Zhang, Yong-Fei Wang, Jing Yang, Jing Zhang, Liangdan Sun, Nattiya Hirankarn, Hai-Feng Pan, Chak Sing Lau, Tak Mao Chan, Tsz Leung Lee, Alexander Moon Ho Leung, Chi Chiu Mok, Lu Zhang, Jiangshan Jane Shen, Sik Nin Wong, Ka Wing Lee, Marco Hok Kung Ho, Pamela Pui Wah Lee, Brian Hon-Yin Chung, Chun Yin Chong, Raymond Woon Sing Wong, Mo Yin Mok, Wilfred Hing Sang Wong, Kwok Lung Tong, Niko Kei Chiu Tse, Xiang-Pei Li, Yingyos Avihingsanon, Pornpimol Rianthavorn, Thavatchai Deekajorndej, Kanya Suphapeetiporn, Vorasuk Shotelersuk, Shirley King Yee Ying, Samuel Ka Shun Fung, Wai Ming Lai, Chun-Ming Wong, Irene Oi Lin Ng, Maria-Merce Garcia-Barcelo, Stacey S Cherny, Paul Kwong-Hang Tam, Pak Chung Sham, Sen Yang, Dong Qing Ye, Yong Cui, Xue-Jun Zhang, Wanling Yang, Yu Lung Lau |
Abstract |
Systemic lupus erythematosus (SLE) is a heterogeneous disease with a diverse spectrum of clinical symptoms from skin rash to end-organ damage. 22q11.21 has been identified as a susceptibility region for several autoimmune diseases, including SLE. However, the detailed information for SLE association and the underlying functional mechanism(s) are still lacking. Through meta-analysis of two genome-wide association studies (GWAS) on Chinese Han populations with a total of 1659 cases and 3398 controls matched geographically, we closely examined this region, especially on the reported single nucleotide polymorphisms (SNPs) associated with different autoimmune diseases and their relationships. We further replicated the most significant association SNP with SLE using 2612 cases and 2323 controls of Asian ancestry. All reported SNPs in this region with different autoimmune diseases were examined in the two GWAS data and meta- analysis result, and supportive evidence of association with SLE was found (meta-analysis P_meta ≤ 7.27E-05), which might require further investigation. SNP rs2298428 was identified as the most significant SNP associated with SLE in this region (P_meta = 2.70E-09). It showed independent effect through both stepwise and conditional logistic regression, and there is no evidence of other independent association signals for SLE in this region. The association of rs2298428 was further replicated in three cohorts from Hong Kong, Anhui and Thailand with a total of 2612 cases and 2323 controls (joint analysis of GWAS and replication result P_all = 1.31E-11, OR = 1.23). SNP rs2298428 was shown to be an eQTL for UBE2L3 gene in different cell types, with the risk allele (T) being correlated with higher expression of UBE2L3. This is consistent with earlier reports on higher expression of UBE2L3 in SLE cases. Association to distinct autoimmune diseases highlights the significance of this region in autoreactive responses and potentially shared functional mechanisms by these diseases. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Germany | 1 | 25% |
Unknown | 3 | 75% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 4 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 40 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 7 | 18% |
Student > Doctoral Student | 4 | 10% |
Student > Master | 3 | 8% |
Student > Ph. D. Student | 3 | 8% |
Lecturer | 2 | 5% |
Other | 5 | 13% |
Unknown | 16 | 40% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 10 | 25% |
Biochemistry, Genetics and Molecular Biology | 4 | 10% |
Immunology and Microbiology | 3 | 8% |
Nursing and Health Professions | 2 | 5% |
Agricultural and Biological Sciences | 1 | 3% |
Other | 1 | 3% |
Unknown | 19 | 48% |