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 patient...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2010-02-01
|
| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC2820522?pdf=render |
| _version_ | 1811261775271690240 |
|---|---|
| author | Wanling Yang Nan Shen Dong-Qing Ye Qiji Liu Yan Zhang Xiao-Xia Qian Nattiya Hirankarn Dingge Ying Hai-Feng Pan Hai-Feng Pan Chi Chiu Mok Tak Mao Chan Raymond Woon Sing Wong Ka Wing Lee Mo Yin Mok Sik Nin Wong Alexander Moon Ho Leung Xiang-Pei Li Yingyos Avihingsanon Chun-Ming Wong Tsz Leung Lee Marco Hok Kung Ho Pamela Pui Wah Lee Yuk Kwan Chang Philip H Li Ruo-Jie Li Lu Zhang Wilfred Hing Sang Wong Irene Oi Lin Ng Chak Sing Lau Pak Chung Sham Yu Lung Lau Asian Lupus Genetics Consortium |
| author_facet | Wanling Yang Nan Shen Dong-Qing Ye Qiji Liu Yan Zhang Xiao-Xia Qian Nattiya Hirankarn Dingge Ying Hai-Feng Pan Hai-Feng Pan Chi Chiu Mok Tak Mao Chan Raymond Woon Sing Wong Ka Wing Lee Mo Yin Mok Sik Nin Wong Alexander Moon Ho Leung Xiang-Pei Li Yingyos Avihingsanon Chun-Ming Wong Tsz Leung Lee Marco Hok Kung Ho Pamela Pui Wah Lee Yuk Kwan Chang Philip H Li Ruo-Jie Li Lu Zhang Wilfred Hing Sang Wong Irene Oi Lin Ng Chak Sing Lau Pak Chung Sham Yu Lung Lau Asian Lupus Genetics Consortium |
| author_sort | Wanling Yang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T19:11:54Z |
| format | Article |
| id | doaj.art-f7db2695f0a04fe5981479e6d3112939 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-12T19:11:54Z |
| publishDate | 2010-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-f7db2695f0a04fe5981479e6d31129392022-12-22T03:19:52ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042010-02-0162e100084110.1371/journal.pgen.1000841Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus.Wanling YangNan ShenDong-Qing YeQiji LiuYan ZhangXiao-Xia QianNattiya HirankarnDingge YingHai-Feng PanHai-Feng PanChi Chiu MokTak Mao ChanRaymond Woon Sing WongKa Wing LeeMo Yin MokSik Nin WongAlexander Moon Ho LeungXiang-Pei LiYingyos AvihingsanonChun-Ming WongTsz Leung LeeMarco Hok Kung HoPamela Pui Wah LeeYuk Kwan ChangPhilip H LiRuo-Jie LiLu ZhangWilfred Hing Sang WongIrene Oi Lin NgChak Sing LauPak Chung ShamYu Lung LauAsian Lupus Genetics ConsortiumSystemic 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.http://europepmc.org/articles/PMC2820522?pdf=render |
| spellingShingle | Wanling Yang Nan Shen Dong-Qing Ye Qiji Liu Yan Zhang Xiao-Xia Qian Nattiya Hirankarn Dingge Ying Hai-Feng Pan Hai-Feng Pan Chi Chiu Mok Tak Mao Chan Raymond Woon Sing Wong Ka Wing Lee Mo Yin Mok Sik Nin Wong Alexander Moon Ho Leung Xiang-Pei Li Yingyos Avihingsanon Chun-Ming Wong Tsz Leung Lee Marco Hok Kung Ho Pamela Pui Wah Lee Yuk Kwan Chang Philip H Li Ruo-Jie Li Lu Zhang Wilfred Hing Sang Wong Irene Oi Lin Ng Chak Sing Lau Pak Chung Sham Yu Lung Lau Asian Lupus Genetics Consortium Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. PLoS Genetics |
| title | Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. |
| title_full | Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. |
| title_fullStr | Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. |
| title_full_unstemmed | Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. |
| title_short | Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. |
| title_sort | genome wide association study in asian populations identifies variants in ets1 and wdfy4 associated with systemic lupus erythematosus |
| url | http://europepmc.org/articles/PMC2820522?pdf=render |
| work_keys_str_mv | AT wanlingyang genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT nanshen genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT dongqingye genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT qijiliu genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT yanzhang genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT xiaoxiaqian genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT nattiyahirankarn genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT dinggeying genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT haifengpan genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT haifengpan genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT chichiumok genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT takmaochan genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT raymondwoonsingwong genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT kawinglee genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT moyinmok genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT sikninwong genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT alexandermoonholeung genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT xiangpeili genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT yingyosavihingsanon genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT chunmingwong genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT tszleunglee genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT marcohokkungho genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT pamelapuiwahlee genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT yukkwanchang genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT philiphli genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT ruojieli genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT luzhang genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT wilfredhingsangwong genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT ireneoilinng genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT chaksinglau genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT pakchungsham genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT yulunglau genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus AT asianlupusgeneticsconsortium genomewideassociationstudyinasianpopulationsidentifiesvariantsinets1andwdfy4associatedwithsystemiclupuserythematosus |