title: Genome-wide association analysis of Vogt-Koyanagi-Harada syndrome identifies two new susceptibility loci at 1p31.2 and 10q21.3.
abstract: To identify new genetic risk factors for Vogt-Koyanagi-Harada (VKH) syndrome, we conducted a genome-wide association study of 2,208,258 SNPs in 774 cases and 2,009 controls with follow-up in a collection of 415 cases and 2,006 controls and a further collection of 349 cases and 1,588 controls from a Han Chinese population. We identified three loci associated with VKH syndrome susceptibility (IL23R-C1orf141, rs117633859, P(combined) = 3.42 × 10(-21), odds ratio (OR) = 1.82; ADO-ZNF365-EGR2, rs442309, P(combined) = 2.97 × 10(-11), OR = 1.37; and HLA-DRB1/DQA1, rs3021304, P(combined) = 1.26 × 10(-118), OR = 2.97). The five non-HLA genes were all expressed in human iris tissue. IL23R was also expressed in the ciliary body, and EGR2 was expressed in the ciliary body and choroid. The risk G allele of rs117633859 in the promoter region of IL23R exhibited low transcriptional activation in a cell-based reporter assay and was associated with diminished IL23R mRNA expression in human peripheral blood mononuclear cells.
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China.
authors.forename: Shengping
authors.initials: S
authors.lastname: Hou
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Du
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Lei
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
authors.forename: Chi Pui
authors.initials: CP
authors.lastname: Pang
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Meifen
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Zhuang
authors.affiliation: Department of Ophthalmology, Xingtai Eye Hospital, Xingtai, China.
authors.forename: Minglian
authors.initials: M
authors.lastname: Zhang
authors.affiliation: The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, China.
authors.forename: Lulin
authors.initials: L
authors.lastname: Huang
authors.affiliation: The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Gong
authors.affiliation: 1] Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China. [2] Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Hu
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China.
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Qi
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China.
authors.forename: Chaokui
authors.initials: C
authors.lastname: Wang
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China. [4] University Clinic for Ophthalmology Maastricht, Maastricht, the Netherlands.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Ye
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liang
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China.
authors.forename: Hongsong
authors.initials: H
authors.lastname: Yu
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Cao
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China.
authors.forename: Yunjia
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Bai
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liao
authors.affiliation: University Clinic for Ophthalmology Maastricht, Maastricht, the Netherlands.
authors.forename: Aize
authors.initials: A
authors.lastname: Kijlstra
authors.affiliation: 1] Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. [2] School of Public Health, Fudan University, Shanghai, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: 1] The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital, Chengdu, China. [2] School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. [3].
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Yang
authors.affiliation: 1] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. [2] Chongqing Key Laboratory of Ophthalmology, Chongqing, China. [3] Chongqing Eye Institute, Chongqing, China. [4].
authors.forename: Peizeng
authors.initials: P
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1; D002879:Chromosomes, Human, Pair 10; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011401:Promoter Regions, Genetic; D014607:Uveomeningoencephalitic Syndrome / Q000235:genetics*
references.citation: Jpn J Ophthalmol. 1994;38(2):208-13
references.pmid: 7967215
references.citation: Nat Genet. 2009 Feb;41(2):199-204
references.pmid: 19169254
references.citation: Invest Ophthalmol Vis Sci. 2013 Nov 21;54(12):7734-8
references.pmid: 24194192
references.citation: Nat Genet. 2010 Nov;42(11):985-90
references.pmid: 20953190
references.citation: Nat Genet. 2010 Apr;42(4):332-7
references.pmid: 20228799
references.citation: Nature. 2007 Jun 7;447(7145):661-78
references.pmid: 17554300
references.citation: Am J Hum Genet. 2007 Sep;81(3):559-75
references.pmid: 17701901
references.citation: Hum Immunol. 2010 Apr;71(4):414-7
references.pmid: 20116410
references.citation: Clin Immunol. 2008 Apr;127(1):43-8
references.pmid: 18282809
references.citation: G3 (Bethesda). 2011 Nov;1(6):457-70
references.pmid: 22384356
references.citation: Invest Ophthalmol Vis Sci. 2011 Sep 09;52(10):7084-9
references.pmid: 21810982
references.citation: PLoS Genet. 2012;8(4):e1002639
references.pmid: 22532805
references.citation: Nat Genet. 2010 Aug;42(8):698-702
references.pmid: 20622878
references.citation: Nat Genet. 2013 Mar;45(3):319-24
references.pmid: 23396137
references.citation: Nat Genet. 2011 Jul 10;43(8):761-7
references.pmid: 21743469
references.citation: Nat Genet. 2010 Aug;42(8):703-6
references.pmid: 20622879
references.citation: Proc Natl Acad Sci U S A. 2013 May 14;110(20):8134-9
references.pmid: 23633568
references.citation: Nat Genet. 2011 Jun 12;43(7):690-4
references.pmid: 21666691
references.citation: Nat Genet. 2007 Nov;39(11):1329-37
references.pmid: 17952073
references.citation: Mol Vis. 2008;14:2597-603
references.pmid: 19122825
references.citation: Ophthalmology. 1995 Jul;102(7):1012-5
references.pmid: 9121744
references.citation: Ann Rheum Dis. 2010 Jul;69(7):1325-8
references.pmid: 20375120
references.citation: Nat Rev Genet. 2004 Apr;5(4):276-87
references.pmid: 15131651
references.citation: Ophthalmology. 2007 Mar;114(3):606-14
references.pmid: 17123618
references.citation: Gut. 2011 Aug;60(8):1060-7
references.pmid: 21257989
references.citation: Nat Genet. 2012 Nov;44(11):1222-6
references.pmid: 23042114
references.citation: Invest Ophthalmol Vis Sci. 1994 Jul;35(8):3234-50
references.pmid: 8045716
references.citation: Am J Hum Genet. 2007 Dec;81(6):1278-83
references.pmid: 17966091
references.citation: Am J Ophthalmol. 2001 May;131(5):647-52
references.pmid: 11336942
references.citation: Nat Genet. 2008 Aug;40(8):955-62
references.pmid: 18587394
references.citation: Am J Hum Genet. 2007 Feb;80(2):273-90
references.pmid: 17236132
references.citation: Surv Ophthalmol. 1995 Jan-Feb;39(4):265-92
references.pmid: 7725227
references.citation: Nat Genet. 2007 May;39(5):596-604
references.pmid: 17435756
references.citation: Arch Ophthalmol. 1991 Mar;109(3):368-70
references.pmid: 2003797
references.citation: Nat Genet. 2009 Feb;41(2):216-20
references.pmid: 19122664
references.citation: Science. 2007 Feb 9;315(5813):848-53
references.pmid: 17289997
references.citation: Am J Ophthalmol. 2000 Feb;129(2):173-7
references.pmid: 10682969
references.citation: Nat Genet. 2011 Mar;43(3):185-7
references.pmid: 21278746
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
references.pmid: 16199517
references.citation: Am J Ophthalmol. 1992 May 15;113(5):567-72
references.pmid: 1575232
references.citation: Invest Ophthalmol Vis Sci. 1994 Oct;35(11):3890-6
references.pmid: 7928186
references.citation: Ann Rheum Dis. 2012 Apr;71 Suppl 2:i96-100
references.pmid: 22460149
references.citation: Nat Genet. 2013 Feb;45(2):202-7
references.pmid: 23291587
references.citation: Immunity. 2012 Oct 19;37(4):685-96
references.pmid: 23021953
references.citation: Pharmacogenomics J. 2014 Apr;14(2):192-200
references.pmid: 23712092
references.citation: Lancet. 1990 May 5;335(8697):1078-80
references.pmid: 1970380
references.citation: Science. 2006 Dec 1;314(5804):1461-3
references.pmid: 17068223
references.citation: Arthritis Rheum. 2012 Aug;64(8):2761-72
references.pmid: 22378604