A Refined Study of FCRL Genes from a Genome-Wide Association Study for Graves’ Disease

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A Refined Study of FCRL Genes from a Genome-Wide Association Study for Graves’ Disease

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Title: A Refined Study of FCRL Genes from a Genome-Wide Association Study for Graves’ Disease
Author: Zhao, Shuang-Xia; Liu, Wei; Zhan, Ming; Song, Zhi-Yi; Yang, Shao-Ying; Xue, Li-Qiong; Pan, Chun-Ming; Gu, Zhao-Hui; Liu, Bing-Li; Wang, Hai-Ning; Liang, Liming; Liang, Jun; Zhang, Xiao-Mei; Yuan, Guo-Yue; Li, Chang-Gui; Chen, Ming-Dao; Chen, Jia-Lun; Gao, Guan-Qi; Song, Huai-Dong

Note: Order does not necessarily reflect citation order of authors.

Citation: Zhao, Shuang-Xia, Wei Liu, Ming Zhan, Zhi-Yi Song, Shao-Ying Yang, Li-Qiong Xue, Chun-Ming Pan, et al. 2013. A refined study of FCRL genes from a genome-wide association study for Graves’ disease. PLoS ONE 8(3): e57758.
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Abstract: To pinpoint the exact location of the etiological variant/s present at 1q21.1 harboring FCRL1-5 and CD5L genes, we carried out a refined association study in the entire FCRL region in 1,536 patients with Graves’ disease (GD) and 1,516 sex-matched controls by imputation analysis, logistic regression, and cis-eQTL analysis. Among 516 SNPs with P<0.05 in the initial GWAS scan, the strongest signals associated with GD and correlated to FCRL3 expression were located at a cluster of SNPs including rs7528684 and rs3761959. And the allele-specific effects for rs3761959 and rs7528684 on FCRL3 expression level revealed that the risk alleles A of rs3761959 and C of rs7528684 were correlated with the elevated expression level of FCRL3 whether in PBMCs or its subsets, especially in \(CD19^+\) B cells and \(CD8^+\) T subsets. Next, the combined analysis with 5,300 GD cases and 4,916 control individuals confirmed FCRL3 was a susceptibility gene of GD in Chinese Han populations, and rs3761959 and rs7528684 met the genome-wide association significance level (\(P_{combined}\) = 2.27×\(10^{−12}\) and 7.11×\(10^{−13}\), respectively). Moreover, the haplotypes with the risk allele A of rs3761959 and risk allele C of rs7528684 were associated with GD risk. Finally, our epigenetic analysis suggested the disease-associated C allele of rs7528684 increased affinity for NF-KB transcription factor. Above data indicated that FCRL3 gene and its proxy SNP rs7528684 may be involved in the pathogenesis of GD by excessive inhibiting B cell receptor signaling and the impairment of suppressing function of Tregs.
Published Version: doi:10.1371/journal.pone.0057758
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591391/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10612885
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