Genome-wide association analysis of Vogt-Koyanagi-Harada syndrome identifies two new susceptibility loci at 1p31.2 and 10q21.3

Shengping Hou; Liping Du; Bo Lei; Chi Pui Pang; Meifen Zhang; Wenjuan Zhuang; Minglian Zhang; Lulin Huang; Bo Gong; Meilin Wang; Qi Zhang; Ke Hu; Qingyun Zhou; Jian Qi; Chaokui Wang; Yuan Tian; Zi Ye; Liang Liang; Hongsong Yu; Hong Li; Yan Zhou; Qingfeng Cao; Yunjia Liu; Lin Bai; Dan Liao; Aize Kijlstra; Jianfeng Xu; Zhenglin Yang; Peizeng Yang

doi:10.1038/ng.3061

Genome-wide association analysis of Vogt-Koyanagi-Harada syndrome identifies two new susceptibility loci at 1p31.2 and 10q21.3

Nat Genet. 2014 Sep;46(9):1007-11. doi: 10.1038/ng.3061. Epub 2014 Aug 10.

Authors

Shengping Hou¹, Liping Du¹, Bo Lei¹, Chi Pui Pang², Meifen Zhang³, Wenjuan Zhuang⁴, Minglian Zhang⁵, Lulin Huang⁶, Bo Gong⁶, Meilin Wang⁷, Qi Zhang¹, Ke Hu¹, Qingyun Zhou¹, Jian Qi¹, Chaokui Wang¹, Yuan Tian⁸, Zi Ye¹, Liang Liang¹, Hongsong Yu¹, Hong Li¹, Yan Zhou¹, Qingfeng Cao¹, Yunjia Liu¹, Lin Bai¹, Dan Liao¹, Aize Kijlstra⁹, Jianfeng Xu¹⁰, Zhenglin Yang¹¹, Peizeng Yang¹²

Affiliations

¹ 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.
² Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China.
³ Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
⁴ Department of Ophthalmology, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, China.
⁵ Department of Ophthalmology, Xingtai Eye Hospital, Xingtai, China.
⁶ 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.
⁷ 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.
⁸ 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.
⁹ University Clinic for Ophthalmology Maastricht, Maastricht, the Netherlands.
¹⁰ 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.
¹¹ 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].
¹² 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].

PMID: 25108386
DOI: 10.1038/ng.3061

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Asian People / genetics
Case-Control Studies
Chromosomes, Human, Pair 1*
Chromosomes, Human, Pair 10*
Female
Genetic Loci*
Genetic Predisposition to Disease
Genome-Wide Association Study / methods
Genotype
Humans
Middle Aged
Polymorphism, Single Nucleotide / genetics
Promoter Regions, Genetic
Uveomeningoencephalitic Syndrome / genetics*