| Autor: |
Xun Chu, Min Shen, Fang Xie, Xiao-Jing Miao, Wei-Hua Shou, Lin Liu, Peng-Peng Yang, Ya-Nan Bai, Kai-Yue Zhang, Lin Yang, Qi Hua, Wen-Dong Liu, Yan Dong, Hai-Feng Wang, Jin-Xiu Shi, Yi Wang, Huai-Dong Song, Sai-Juan Chen, Zhu Chen, Wei Huang |
| Předmět: |
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| Zdroj: |
Journal of Medical Genetics; Jul2013, Vol. 50 Issue 7, p479-485, 7p, 2 Charts, 2 Graphs |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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