Genome-Wide Association Study in Asian Populations Identifies Variants in ETS1 and WDFY4 Associated with Systemic Lupus Erythematosus


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.

DOI: 10.1371/journal.pgen.1000841

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@inproceedings{Yang2010GenomeWideAS, title={Genome-Wide Association Study in Asian Populations Identifies Variants in ETS1 and WDFY4 Associated with Systemic Lupus Erythematosus}, author={Wanling Yang and Nan Shen and Dong Ye and Qi-ji Liu and Yan Zhang and X. Qian and Nattiya Hirankarn and Dingge Ying and Hai-Feng Pan and Chi Chiu Mok and Tak Mao Chan and Raymond Woon Sing Wong and Ka Wing Lee and M Y Mok and Sik Nin Wong and Alexander Moon Ho Leung and Xiang-pei Li and Yingyos Avihingsanon and Chun-Ming Wong and Tsz Leung Lee and Marco Hok Kung Ho and Pamela Lee and Yuk Kwan Chang and Philip Hei Li and Ruo-jie Li and Lu Zhang and Wilfred Hing Sang Wong and Irene Oi - Lin Ng and C S Lau and Pak Chung Sham and Yu Lung Lau}, booktitle={PLoS genetics}, year={2010} }