TY - JOUR
T1 - Genome-wide association analysis of Vogt-Koyanagi-Harada syndrome identifies two new susceptibility loci at 1p31.2 and 10q21.3
AU - Hou, Shengping
AU - Du, Liping
AU - Lei, Bo
AU - Pang, Chi Pui
AU - Zhang, Meifen
AU - Zhuang, Wenjuan
AU - Zhang, Minglian
AU - Huang, Lulin
AU - Gong, Bo
AU - Wang, Meilin
AU - Zhang, Qi
AU - Hu, Ke
AU - Zhou, Qingyun
AU - Qi, Jian
AU - Wang, Chaokui
AU - Tian, Yuan
AU - Ye, Zi
AU - Liang, Liang
AU - Yu, Hongsong
AU - Li, Hong
AU - Zhou, Yan
AU - Cao, Qingfeng
AU - Liu, Yunjia
AU - Bai, Lin
AU - Liao, Dan
AU - Kijlstra, Aize
AU - Xu, Jianfeng
AU - Yang, Zhenglin
AU - Yang, Peizeng
PY - 2014/9
Y1 - 2014/9
N2 - 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.
AB - 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.
U2 - 10.1038/ng.3061
DO - 10.1038/ng.3061
M3 - Article
C2 - 25108386
SN - 1061-4036
VL - 46
SP - 1007
EP - 1011
JO - Nature Genetics
JF - Nature Genetics
IS - 9
ER -