title: Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus.
abstract: Systemic lupus erythematosus is a complex and potentially fatal autoimmune disease, characterized by autoantibody production and multi-organ damage. By a genome-wide association study (320 patients and 1,500 controls) and subsequent replication altogether involving a total of 3,300 Asian SLE patients from Hong Kong, Mainland China, and Thailand, as well as 4,200 ethnically and geographically matched controls, genetic variants in ETS1 and WDFY4 were found to be associated with SLE (ETS1: rs1128334, P = 2.33x10(-11), OR = 1.29; WDFY4: rs7097397, P = 8.15x10(-12), OR = 1.30). ETS1 encodes for a transcription factor known to be involved in a wide range of immune functions, including Th17 cell development and terminal differentiation of B lymphocytes. SNP rs1128334 is located in the 3'-UTR of ETS1, and allelic expression analysis from peripheral blood mononuclear cells showed significantly lower expression level from the risk allele. WDFY4 is a conserved protein with unknown function, but is predominantly expressed in primary and secondary immune tissues, and rs7097397 in WDFY4 changes an arginine residue to glutamine (R1816Q) in this protein. Our study also confirmed association of the HLA locus, STAT4, TNFSF4, BLK, BANK1, IRF5, and TNFAIP3 with SLE in Asians. These new genetic findings may help us to gain a better understanding of the disease and the functions of the genes involved.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.
authors.forename: Wanling
authors.initials: W
authors.lastname: Yang
authors.forename: Nan
authors.initials: N
authors.lastname: Shen
authors.forename: Dong-Qing
authors.initials: DQ
authors.lastname: Ye
authors.forename: Qiji
authors.initials: Q
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Qian
authors.forename: Nattiya
authors.initials: N
authors.lastname: Hirankarn
authors.forename: Dingge
authors.initials: D
authors.lastname: Ying
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Pan
authors.forename: Chi Chiu
authors.initials: CC
authors.lastname: Mok
authors.forename: Tak Mao
authors.initials: TM
authors.lastname: Chan
authors.forename: Raymond Woon Sing
authors.initials: RW
authors.lastname: Wong
authors.forename: Ka Wing
authors.initials: KW
authors.lastname: Lee
authors.forename: Mo Yin
authors.initials: MY
authors.lastname: Mok
authors.forename: Sik Nin
authors.initials: SN
authors.lastname: Wong
authors.forename: Alexander Moon Ho
authors.initials: AM
authors.lastname: Leung
authors.forename: Xiang-Pei
authors.initials: XP
authors.lastname: Li
authors.forename: Yingyos
authors.initials: Y
authors.lastname: Avihingsanon
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Wong
authors.forename: Tsz Leung
authors.initials: TL
authors.lastname: Lee
authors.forename: Marco Hok Kung
authors.initials: MH
authors.lastname: Ho
authors.forename: Pamela Pui Wah
authors.initials: PP
authors.lastname: Lee
authors.forename: Yuk Kwan
authors.initials: YK
authors.lastname: Chang
authors.forename: Philip H
authors.initials: PH
authors.lastname: Li
authors.forename: Ruo-Jie
authors.initials: RJ
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Wilfred Hing Sang
authors.initials: WH
authors.lastname: Wong
authors.forename: Irene Oi Lin
authors.initials: IO
authors.lastname: Ng
authors.forename: Chak Sing
authors.initials: CS
authors.lastname: Lau
authors.forename: Pak Chung
authors.initials: PC
authors.lastname: Sham
authors.forename: Yu Lung
authors.initials: YL
authors.lastname: Lau
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D015331:Cohort Studies; D004268:DNA-Binding Proteins; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D015810:Linkage Disequilibrium / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis; D050784:Proto-Oncogene Protein c-ets-1 / Q000235:genetics*; D015203:Reproducibility of Results; D050797:STAT4 Transcription Factor / Q000235:genetics; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D019061:src-Family Kinases / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C447641:BANK1 protein, human; D004268:DNA-Binding Proteins; C494041:ETS1 protein, human; C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D050784:Proto-Oncogene Protein c-ets-1; D050797:STAT4 Transcription Factor; C549018:WDFY4 protein, human; C082599:protein-tyrosine kinase p55(blk); D019061:src-Family Kinases; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3