Integrative analysis of genome‐wide association study and expression quantitative trait loci datasets identified various immune cell‐related pathways for rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is an autoimmune chronic disorder manifesting as warm, swollen, and painful joints. Multiple immune cells are implicated in the development of RA. Previous studies demonstrated that integrating the genetic information of genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) is capable of identifying new disease-risk loci and providing novel insights into the etiology of complex human disease. In this study, we conducted an integrative pathway association analysis of RA by using GWAS summary data and five immune cell types related to eQTL datasets of RA. After combining the cell-specific eQTLs and GWAS summary of RA and performing a pathway-enrichment analysis, we detected a group of RA-associated pathways with common or cell-specific enriched in the five immune cell types. 41 pathways for B cells, 33 pathways for CD4 +

Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target

“…In addition, GWAS have identified ~100 non-HLA loci, including TNF, associated with RA. GWAS data also suggest the involvement of multiple immune cell types, including T cells, B cells, natural killer cells, dendritic cells and monocytes, as well as the pro-inflammatory cytokines produced by these cells, in mediating RA pathogenesis 93 . Interestingly, SNPs and reduced levels of TNFAIP3 have been associated with RA 94 .…”

N6-Methyladenosine and Rheumatoid Arthritis: A Comprehensive Review

“…NK cells are natural immune effector cells with a direct killing function and are particularly important in immune cells because they eliminate viral infections and secrete proinflammatory cytokines. Li et al conducted an integrative pathway association analysis of RA using genome-wide association studies (GWAS) summary data of 25 RA-associated pathways for NK cells (2). A large number of NK cells were found in the synovial fluid of RA patients, which is considered an important factor for bone destruction (101).…”

“…FLS cells are the primary synovial cells, which secrete inflammatory cytokines, chemokines, and metalloproteinases (1). Furthermore, inflammatory cytokines interact with immune cells that are related to RA, such as macrophages, natural killer (NK) cells, dendritic cells (DC), lymphocytes, and mast cells (MCs) (2). Currently, non-steroidal anti-inflammatory drugs and immunosuppressants are commonly used in clinical practice to alleviate the prevent the development of RA.…”

Causal risk and protective factors in rheumatoid arthritis: A genetic update

“…The ACPA positive subgroup includes an association with PTPN22 rs2476601 (OR = 1.91; IC95: 1.77–2.05) and IL-6R rs12083537, while the ACPA negative subgroup comprises associations with BLK (rs4840565: OR = 1.12; CI95: 1.01–1.24), STAT4 (rs10181656: OR = 1.04; IC95: 0.93–1.16), and IRF5 [ 78 , 79 ]. Genome wide association studies (GWAS) coupled with an epigenetic approach have further implicated genes important for common or cell specific pathways for B cells, CD4 and CD8 T cells, monocytes and natural killer [ 80 , 81 ].…”