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Article: Genome-wide association study in asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus

TitleGenome-wide association study in asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus
Authors
Issue Date2010
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/
Citation
Plos Genetics, 2010, v. 6 n. 2 How to Cite?
AbstractSystemic 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. © 2010 Yang et al.
Persistent Identifierhttp://hdl.handle.net/10722/123949
ISSN
2014 Impact Factor: 7.528
2014 SCImago Journal Rankings: 5.792
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council of the Hong Kong GovernmentGRF HKU781709M
Dr Cheng Yu Tung's Fellowship, University of Hong Kong
Edward the Sai Kim Hotung Paediatric Education and Research Fund
University Postgraduate Studentship
National Basic Research Program of China2007CB947900
National High Technology Research and Development Program of China2007AA02Z123
National Natural Science Foundation of China30700734
30830089
Key Basic Program of the Shanghai Commission of Science and Technology06JC14050
08JC1414700
Program of Shanghai Subject07XD14021
National Research Council of Thailand
Funding Information:

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.

References

 

DC FieldValueLanguage
dc.contributor.authorYang, Wen_HK
dc.contributor.authorShen, Nen_HK
dc.contributor.authorYe, DQen_HK
dc.contributor.authorLiu, Qen_HK
dc.contributor.authorZhang, Yen_HK
dc.contributor.authorQian, XXen_HK
dc.contributor.authorHirankarn, Nen_HK
dc.contributor.authorYing, Den_HK
dc.contributor.authorPan, HFen_HK
dc.contributor.authorMok, CCen_HK
dc.contributor.authorChan, TMen_HK
dc.contributor.authorWong, RWSen_HK
dc.contributor.authorLee, KWen_HK
dc.contributor.authorMok, MYen_HK
dc.contributor.authorWong, SNen_HK
dc.contributor.authorLeung, AMHen_HK
dc.contributor.authorLi, XPen_HK
dc.contributor.authorAvihingsanon, Yen_HK
dc.contributor.authorWong, CMen_HK
dc.contributor.authorLee, TLen_HK
dc.contributor.authorHo, MHKen_HK
dc.contributor.authorLee, PPWen_HK
dc.contributor.authorChang, YKen_HK
dc.contributor.authorLi, PHen_HK
dc.contributor.authorLi, RJen_HK
dc.contributor.authorZhang, Len_HK
dc.contributor.authorWong, WHSen_HK
dc.contributor.authorNg, IOLen_HK
dc.contributor.authorLau, CSen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorLau, YLen_HK
dc.date.accessioned2010-10-12T08:59:28Z-
dc.date.available2010-10-12T08:59:28Z-
dc.date.issued2010en_HK
dc.identifier.citationPlos Genetics, 2010, v. 6 n. 2en_HK
dc.identifier.issn1553-7390en_HK
dc.identifier.urihttp://hdl.handle.net/10722/123949-
dc.description.abstractSystemic 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. © 2010 Yang et al.en_HK
dc.languageeng-
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosgenetics.org/en_HK
dc.relation.ispartofPLoS Geneticsen_HK
dc.subject.meshAsian Continental Ancestry Group - genetics-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGenome-Wide Association Study-
dc.subject.meshIntracellular Signaling Peptides and Proteins - genetics-
dc.subject.meshLupus Erythematosus, Systemic - enzymology - genetics-
dc.titleGenome-wide association study in asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosusen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1553-7390&volume=6&issue=2 article no. e1000841&spage=&epage=&date=2010&atitle=Genome-wide+association+study+in+Asian+populations+identifies+variants+in+ETS1+and+WDFY4+associated+with+systemic+lupus+erythematosus-
dc.identifier.emailYang, W: yangwl@hkucc.hku.hken_HK
dc.identifier.emailChan, TM: dtmchan@hku.hken_HK
dc.identifier.emailMok, MY: temy@hkucc.hku.hken_HK
dc.identifier.emailWong, CM: jcmwong@hkucc.hku.hken_HK
dc.identifier.emailLee, PPW: ppwlee@hku.hken_HK
dc.identifier.emailNg, IOL: iolng@hku.hken_HK
dc.identifier.emailLau, CS: cslau@hku.hken_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.emailLau, YL: lauylung@hku.hken_HK
dc.identifier.authorityYang, W=rp00524en_HK
dc.identifier.authorityChan, TM=rp00394en_HK
dc.identifier.authorityMok, MY=rp00490en_HK
dc.identifier.authorityWong, CM=rp00231en_HK
dc.identifier.authorityLee, PPW=rp00462en_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.identifier.authorityLau, CS=rp01348en_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.identifier.authorityLau, YL=rp00361en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1371/journal.pgen.1000841en_HK
dc.identifier.pmid20169177-
dc.identifier.pmcidPMC2820522-
dc.identifier.scopuseid_2-s2.0-77649206245en_HK
dc.identifier.hkuros170267-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77649206245&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue2en_HK
dc.identifier.eissn1553-7404-
dc.identifier.isiWOS:000275262700021-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridYang, W=23101349500en_HK
dc.identifier.scopusauthoridShen, N=7102785475en_HK
dc.identifier.scopusauthoridYe, DQ=24588340700en_HK
dc.identifier.scopusauthoridLiu, Q=7406292285en_HK
dc.identifier.scopusauthoridZhang, Y=35789432400en_HK
dc.identifier.scopusauthoridQian, XX=36572441800en_HK
dc.identifier.scopusauthoridHirankarn, N=12783320200en_HK
dc.identifier.scopusauthoridYing, D=35197469900en_HK
dc.identifier.scopusauthoridPan, HF=35234356200en_HK
dc.identifier.scopusauthoridMok, CC=34668219600en_HK
dc.identifier.scopusauthoridChan, TM=7402687700en_HK
dc.identifier.scopusauthoridWong, RWS=34875928200en_HK
dc.identifier.scopusauthoridLee, KW=35788977700en_HK
dc.identifier.scopusauthoridMok, MY=7006024184en_HK
dc.identifier.scopusauthoridWong, SN=7404590305en_HK
dc.identifier.scopusauthoridLeung, AMH=35788888900en_HK
dc.identifier.scopusauthoridLi, XP=35237897300en_HK
dc.identifier.scopusauthoridAvihingsanon, Y=6506712307en_HK
dc.identifier.scopusauthoridWong, CM=16314668400en_HK
dc.identifier.scopusauthoridLee, TL=55345848300en_HK
dc.identifier.scopusauthoridHo, MHK=8925896400en_HK
dc.identifier.scopusauthoridLee, PPW=14048822200en_HK
dc.identifier.scopusauthoridChang, YK=35788792500en_HK
dc.identifier.scopusauthoridLi, PH=35788992300en_HK
dc.identifier.scopusauthoridLi, RJ=35788882900en_HK
dc.identifier.scopusauthoridZhang, L=36012071400en_HK
dc.identifier.scopusauthoridWong, WHS=13310222200en_HK
dc.identifier.scopusauthoridNg, IOL=7102753722en_HK
dc.identifier.scopusauthoridLau, CS=14035682100en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.scopusauthoridLau, YL=7201403380en_HK
dc.identifier.citeulike7100928-

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