Genetic architecture study of rheumatoid arthritis and juvenile idiopathic arthritis

PeerJ. 2020 Jan 15;8:e8234. doi: 10.7717/peerj.8234. eCollection 2020.


Background: Rheumatoid arthritis and juvenile idiopathic arthritis are two types of autoimmune diseases with inflammation at the joints, occurring to adults and children respectively. There are phenotypic overlaps between these two types of diseases, despite the age difference in patient groups.

Methods: To systematically compare the genetic architecture of them, we conducted analyses at gene and pathway levels and constructed protein-protein-interaction network based on summary statistics of genome-wide association studies of these two diseases. We examined their difference and similarity at each level.

Results: We observed extensive overlap in significant SNPs and genes at the human leukocyte antigen region. In addition, several SNPs in other regions of the human genome were also significantly associated with both diseases. We found significantly associated genes enriched in 32 pathways shared by both diseases. Excluding genes in the human leukocyte antigen region, significant enrichment is present for pathways like interleukin-27 pathway and NO2-dependent interleukin-12 pathway in natural killer cells.

Discussion: The identification of commonly associated genes and pathways may help in finding population at risk for both diseases, as well as shed light on repositioning and designing drugs for both diseases.

Keywords: Genetic architecture comparison; Genome-wide association studies; Juvenile idiopathic arthritis; Pathway enrichment; Rheumatoid arthritis.

Grant support

This study was supported by National Natural Science Foundation of China (No.81771769), Tianjin Natural Science Foundation (No.18JCYBJC42700), Startup Funding from Tianjin Medical University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.