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A refined study of FCRL genes from a genome-wide association study for Graves' disease.

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.

SUBMITTER: Zhao SX

PROVIDER: S-EPMC3591391 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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A refined study of FCRL genes from a genome-wide association study for Graves' disease.

Zhao Shuang-Xia SX Liu Wei W Zhan Ming M Song Zhi-Yi ZY Yang Shao-Ying SY Xue Li-Qiong LQ Pan Chun-Ming CM Gu Zhao-Hui ZH Liu Bing-Li BL Wang Hai-Ning HN Liang Liming L Liang Jun J Zhang Xiao-Mei XM Yuan Guo-Yue GY Li Chang-Gui CG Chen Ming-Dao MD Chen Jia-Lun JL Gao Guan-Qi GQ Song Huai-Dong HD

PloS one 20130307 3

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 rs7 ...[more]

PMID: 23505439

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Dataset Information

A refined study of FCRL genes from a genome-wide association study for Graves' disease.

Publications

A refined study of FCRL genes from a genome-wide association study for Graves' disease.

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