Enrichment analysis of associated disease and circadian genes in rheumatoid arthritis

Genomics England Research Registry ID: 1090

Registered: 25/03/2024

Expert summary

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory autoimmune disease characterised by synovial hyperplasia, cartilage and subchondral bone destruction, and symptoms such as morning stiffness and joint pain. RA presents with a circadian phenotype (morning stiffness) and a seasonal phenotype, correlated with heightened disease symptoms in the winter. The RA cohort will be created by filtering by the presence of the HPO term (HP:0001370) within the rare disease cohort. The control cohort will be filtered by the absence of the HPO term within the cohort. Using variants associated with RA extracted from the GWAS catalogue and the literature, the genomic coordinates will be extracted from the genomes of the RA cohort and undergo enrichment analysis using logistic regression and Fishers test. The odds ratio obtained from the enrichment analysis will also be compared to the odds ratio of the variants from the GWAS catalogue and the literature for further analysis and interpretation.

Lay summary

Rheumatoid arthritis (RA) is an autoimmune joint disease which results in considerable joint inflammation, pain, and stiffness. Individuals with RA typically experience worse symptoms in the morning (e.g. increased stiffness) which implies that there is a circadian (body clock) involvement. This research aims to gather a list of variants associated with RA using the literature and the GWAS catalogue, and analyse how prevalent these variants are in the genomes of participants with RA in the 100,000 genomes cohort. This will be compared to a ‘control’ cohort, which are participants who do not have RA. The frequency of the mutations/variants in the two cohorts will be compared. Further analysis on this data will include if these variants are more common in individuals with RA, or if they are more common in the general population.