Integrative analysis of genome-wide association study and expression quantitative trait loci datasets identified...

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⁺ T cells, 27 pathways for CD8⁺ T cells, 39 pathways for monocyte, and 25 pathways for natural killer cells are significant in RA, among which 48% are common pathways and 32% are cell-specific pathways. We detected a group of RA-associated eQTL pathways related to five different immune cell types. Our findings may provide novel insights into the pathogenesis of RA.