Open AccessGenome-wide association studies and gene expression profiles of rheumatoid arthritis
Author(s) -
Xue Xiao,
Jingcan Hao,
Yan Wen,
W. Wang,
Xiong Guo,
Feng Zhang
Publication year - 2016
Publication title -
bone and joint research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.639
H-Index - 31
ISSN - 2046-3758
DOI - 10.1302/2046-3758.57.2000502
Subject(s) - genome wide association study , human leukocyte antigen , gene , genetic association , rheumatoid arthritis , gene expression , antigen processing , cd63 , biology , major histocompatibility complex , antigen , genetics , medicine , computational biology , immunology , single nucleotide polymorphism , mhc class i , genotype , microrna , microvesicles
Objectives The molecular mechanism of rheumatoid arthritis (RA) remains elusive. We conducted a protein-protein interaction network-based integrative analysis of genome-wide association studies (GWAS) and gene expression profiles of RA.Methods We first performed a dense search of RA-associated gene modules by integrating a large GWAS meta-analysis dataset (containing 5539 RA patients and 20 169 healthy controls), protein interaction network and gene expression profiles of RA synovium and peripheral blood mononuclear cells (PBMCs). Gene ontology (GO) enrichment analysis was conducted by DAVID. The protein association networks of gene modules were generated by STRING.Results For RA synovium, the top-ranked gene module is HLA-A, containing TAP2, HLA-A, HLA-C, TAPBP and LILRB1 genes. For RA PBMCs, the top-ranked gene module is GRB7, consisting of HLA-DRB5, HLA-DRA, GRB7, CD63 and KIT genes. Functional enrichment analysis identified three significant GO terms for RA synovium, including antigen processing and presentation of peptide antigen via major histocompatibility complex class I (false discovery rate (FDR) = 4.86 × 10 – 4), antigen processing and presentation of peptide antigen (FDR = 2.33 × 10 – 3) and eukaryotic translation initiation factor 4F complex (FDR = 2.52 × 10 – 2).Conclusion This study reported several RA-associated gene modules and their functional association networks. Cite this article: X. Xiao, J. Hao, Y. Wen, W. Wang, X. Guo, F. Zhang. Genome-wide association studies and gene expression profiles of rheumatoid arthritis: an analysis. Bone Joint Res 2016;5:314–319. DOI: 10.1302/2046-3758.57.2000502.