RT Journal Article
SR Electronic
T1 An X chromosome-wide association analysis identifies variants in <em>GPR174</em> as a risk factor for Graves’ disease
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 479
OP 485
DO 10.1136/jmedgenet-2013-101595
VO 50
IS 7
A1 Xun Chu
A1 Min Shen
A1 Fang Xie
A1 Xiao-Jing Miao
A1 Wei-Hua Shou
A1 Lin Liu
A1 Peng-Peng Yang
A1 Ya-Nan Bai
A1 Kai-Yue Zhang
A1 Lin Yang
A1 Qi Hua
A1 Wen-Dong Liu
A1 Yan Dong
A1 Hai-Feng Wang
A1 Jin-Xiu Shi
A1 Yi Wang
A1 Huai-Dong Song
A1 Sai-Juan Chen
A1 Zhu Chen
A1 Wei Huang
YR 2013
UL http://jmg.bmj.com/content/50/7/479.abstract
AB Background Graves’ disease is a female preponderant autoimmune illness and the contribution of the X chromosome to its risk has long been appreciated. However, no X-linked susceptibility loci have been indentified from recent genome-wide association studies (GWAS). Methods We re-examined the X chromosome data from our recent GWAS for Graves’ disease by including males that were previously excluded from the X chromosome analyses. The data were analysed using logistic regression analysis including sex as a covariate, and an additive method assuming X chromosome inactivation, implemented in snpMatrix. Results A cluster of single nucleotide polymorphism (SNPs) at Xq21.1 was found showing association with genome-wide significance, among which rs3827440 was a non-synonymous SNP of GPR174 (Plogistic regression= 9.52×10−8; PsnpMatrix=4.60×10−9; OR=1.76, 95% CI 1.45 to 2.13). The association was reproduced in an independent sample collection set including 4564 Graves’ disease cases and 3968 sex matched controls (combined Plogistic regression=5.53×10−21; combined PsnpMatrix=4.26×10−22; OR=1.69, 95% CI 1.53 to 1.86). Notably, GPR174 was widely expressed in immune related tissues and rs3827440 genotypes were associated with distinct mRNA levels (p=0.002). GPR174 did not show sex biased gene expression in our expression analysis. Resequencing study suggested the contribution of some rare variants in the GPR174 gene region to disease risk with a collapsing p value of 1.16×10−3. Conclusions The finding of an X-linked risk locus for Graves’ disease expands our understanding of the role of the X chromosome in disease susceptibility.