| Title | Exome-wide association study identifies four novel loci for systemic lupus erythematosus in Han Chinese population |
| Authors | Wen, Leilei Zhu, Caihong Zhu, Zhengwei Yang, Chao Zheng, Xiaodong Liu, Lu Zuo, Xianbo Sheng, Yujun Tang, Huayang Liang, Bo Zhou, Yi Li, Pan Zhu, Jun Ding, Yantao Chen, Gang Gao, Jinping Tang, Lili Cheng, Yuyan Sun, Jingying Elango, Tamilselvi Kafle, Anjana Yu, Ruixing Xue, Ke Zhang, Yaohua Li, Feng Li, Zhanguo Guo, Jianping Zhang, Xuan Zhou, Chen Tang, Yuanjia Shen, Nan Wang, Meng Yu, Xueqing Liu, Shengxiu Fan, Xing Gao, Min Xiao, Fengli Wang, Peiguang Wang, Zaixing Zhang, Anping Zhou, Fusheng Sun, Liangdan |
| Affiliation | Fudan Univ, Huashan Hosp, Inst Dermatol, Dept Dermatol, Shanghai 200040, Peoples R China. Anhui Med Univ, Dept Dermatol, Affiliated Hosp 1, Key Lab Dermatol,Minist Educ, Hefei, Anhui, Peoples R China. China Japan Friendship Hosp, Dept Dermatol, Beijing, Peoples R China. Peking Univ, Dept Rheumatol & Immunol, Peoples Hosp, Beijing, Peoples R China. Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Rheumatol & Clin Immunol, Beijing, Peoples R China. Peking Union Med Coll, Beijing, Peoples R China. Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Inst Rheumatol, Shanghai, Peoples R China. Sun Yat Sen Univ, Key Lab Nephrol, Minist Hlth, Dept Nephrol,Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China. Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. Anhui Med Univ, Minist Educ, Key Lab Dermatol, Hefei, Anhui, Peoples R China. Yin, XY Zhang, XJ (reprint author), Fudan Univ, Huashan Hosp, Inst Dermatol, Dept Dermatol, Shanghai 200040, Peoples R China. Cui, Y Zhang, XJ (reprint author), China Japan Friendship Hosp, Dept Dermatol, Beijing, Peoples R China. |
| Keywords | autoimmune diseases,gene polymorphism,systemic lupus erythematosus GENE-EXPRESSION IMMUNE CELLS VARIANTS DISEASE TACI METAANALYSIS INDIVIDUALS ACTIVATION INTERFERON SCLEROSIS |
| Issue Date | 2018 |
| Publisher | ANNALS OF THE RHEUMATIC DISEASES |
| Citation | ANNALS OF THE RHEUMATIC DISEASES. 2018, 77(3). |
| Abstract | Objectives Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of considerable genetic predisposition. Genome-wide association studies have identified tens of common variants for SLE. However, the majority of them reside in non-coding sequences. The contributions of coding variants have not yet been systematically evaluated. Methods We performed a large-scale exome-wide study in 5004 SLE cases and 8179 healthy controls in a Han Chinese population using a custom exome array, and then genotyped 32 variants with suggestive evidence in an independent cohort of 13 246 samples. We further explored the regulatory effect of one novel non-coding single nucleotide polymorphism (SNP) in ex vivo experiments. Results We discovered four novel SLE gene regions (LCT, TPCN2, AHNAK2 and TNFRSF13B) encompassing three novel missense variants (XP_016859577.1: p.Asn1639Ser, XP_016859577.1: p.Val219Phe and XP_005267356.1: p.Thr4664Ala) and two non-coding variants (rs10750836 and rs4792801) with genomewide significance (p meta <5.00x10(-8)). These variants are enriched in several chromatin states of primary B cells. The novel intergenic variant rs10750836 exhibited an expression quantitative trait locus effect on the TPCN2 gene in immune cells. Clones containing this novel SNP exhibited gene promoter activity for TPCN2 (P=1.38x10(-3)) whose expression level was reduced significantly in patients with SLE (P<2.53x10(-2)) and was suggested to be further modulated by rs10750836 in CD19+B cells (P=7.57x10(-5)) in ex vivo experiments. Conclusions This study identified three novel coding variants and four new susceptibility gene regions for SLE. The results provide insights into the biological mechanism of SLE. |
| URI | http://hdl.handle.net/20.500.11897/502747 |
| ISSN | 0003-4967 |
| DOI | 10.1136/annrheumdis-2017-211823 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 人民医院 |
