This study was undertaken to investigate the hypothesis that a genetic predisposition toward rheumatoid arthritis (RA) increases the risk of 10 cardiometabolic and autoimmune disorders previously associated with RA in epidemiologic studies, and to define new genetic pleiotropy present in RA.
Two approaches were used to test our hypothesis. First, we constructed a weighted genetic risk score (wGRS) and then examined its association with 10 prespecified disorders. Additionally, a phenome-wide association study (PheWAS) was carried out to identify potential new associations. Second, inverse variance-weighted regression (IVWR) meta-analysis was used to characterize the association between genetic susceptibility to RA and the prespecified disorders, with the results expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs).
The wGRS for RA was significantly associated with type 1 diabetes mellitus (DM) (OR 1.10 [95% CI 1.04-1.16]; P = 9.82 × 10
This study presents evidence of pleiotropy between the genetic predisposition to RA and associated phenotypes found in other autoimmune and cardiometabolic disorders, including type 1 DM.