An X chromosome-wide association analysis identifies variants in GPR174 as a risk factor to Graves’ disease

Graves’ disease is an autoimmune illness mostly seen in female. The contribution of the X chromosomes to its risk has long been appreciated. We re-examined the X chromosome data from our recent study using a technology named genome-wide association study (GWAS). A single nucleotide polymorphism (SNP) which changes an amino acid within the G protein-coupled receptor 174 gene (GPR174)  on Xq21.1, namely rs3827440, was associated with susceptibility to Graves’ disease and the odds ratio was next to that of the HLA SNPs, the previously established most significant locus related to this disease. Resequencing results revealed other rare variants of GPR174 also contributed to disease risk. GPR174 is widely expressed in immune-related tissues and might serve as a potential drug target in future studies. The finding of an X-linked risk locus for Graves’ disease expands our understanding of the role played by X chromosome in the pathogenesis of autoimmune diseases. (Professor Wei Huang, http://jmg.bmj.com/content/early/2013/05/09/jmedgenet-2013-101595 )