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

• Published in: Nature genetics Vol. 46; no. 9; pp. 1007 - 1011
• Main Authors: Hou, Shengping, Du, Liping, Lei, Bo, Pang, Chi Pui, Zhang, Meifen, Zhuang, Wenjuan, Zhang, Minglian, Huang, Lulin, Gong, Bo, Wang, Meilin, Zhang, Qi, Hu, Ke, Zhou, Qingyun, Qi, Jian, Wang, Chaokui, Tian, Yuan, Ye, Zi, Liang, Liang, Yu, Hongsong, Li, Hong, Zhou, Yan, Cao, Qingfeng, Liu, Yunjia, Bai, Lin, Liao, Dan, Kijlstra, Aize, Xu, Jianfeng, Yang, Zhenglin, Yang, Peizeng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2014; Nature Publishing Group
• Subjects: 38/43; 45; 45/61; 692/699; Adult; Aged; Agriculture; Analysis; Animal Genetics and Genomics; Asian Continental Ancestry Group - genetics; Autoimmune diseases; Biomedicine; Cancer Research; Case-Control Studies; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 10; Disease susceptibility; Female; Gene expression; Gene Function; Genes; Genetic aspects; Genetic Loci; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study - methods; Genomes; Genomics; Genotype; Human Genetics; Humans; Identification and classification; letter; Messenger RNA; Methods; Middle Aged; Polymorphism, Single Nucleotide - genetics; Principal components analysis; Promoter Regions, Genetic; Quantitative trait loci; Risk factors; RNA; Signal transduction; Software; Uveomeningoencephalitic Syndrome - genetics
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng.3061

Peizeng Yang, Zhenglin Yang and colleagues report results of a genome-wide association study of Vogt-Koyanagi-Harada syndrome. They confirm strong association with the HLA region and identify two new susceptibility loci, including variants near IL23R . 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.