Title Genome-wide association study in asian populations identifies variants in ETS 1 and WDFY 4 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 = 2.33610, OR = 1.29; WDFY4: rs7097397, P = 8.15610, 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 39-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. Citation: Yang W, Shen N, Ye D-Q, Liu Q, Zhang Y, et al. (2010) Genome-Wide Association Study in Asian Populations Identifies Variants in ETS1 and WDFY4 Associated with Systemic Lupus Erythematosus. PLoS Genet 6(2): e1000841. doi:10.1371/journal.pgen. 1000841 Editor: Jonathan Flint, The Wellcome Trust Centre for Human Genetics, University of Oxford, United Kingdom Received October 23, 2009; Accepted January 11, 2010; Published February 12, 2010 Copyright: 2010 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This study was partially supported by the generous donation from Shun Tak District Min Yuen Tong of Hong Kong (to YLL). WY thanks support from Research Grant Council of the Hong Kong Government (GRF HKU781709M). QL was supported by Dr Cheng Yu Tung’s Fellowship through the Faculty of Medicine, University of Hong Kong. YZ is supported by Edward the Sai Kim Hotung Paediatric Education and Research Fund and University Postgraduate Studentship. NS thanks grant support from the following funding agencies: National Basic Research Program of China (2007CB947900), National High Technology Research and Development Program of China (2007AA02Z123), National Natural Science Foundation of China (30700734), Key Basic Program of the Shanghai Commission of Science and Technology (06JC14050, 08JC1414700), and Program of Shanghai Subject Chief Scientist (07XD14021). DQY thanks grant support from the key program of National Natural Science Foundation of China (No. 30830089). NH and YA thank support from the National Research Council of Thailand. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: lauylung@hkucc.hku. hk " Membership of the Asian Lupus Genetics Consortium is provided in the Acknowledgments.