Fig. 3.

Estimated effects of genetic variation(s) in antidiabetic drug targets on seropositive rheumatoid arthritis. OR, odds ratio; CI, confidence interval; RA, rheumatoid arthritis. * The rs1801282 variant is a functional variant within the PPARG gene region and can regulate binding affinity to PPARγ (encoded by the PPARG gene) response element and ability to activate transcription. † The rs757110 variant is a functional variant within the ABCC8 gene. It can promote insulin release by inhibiting ATP-sensitive potassium channel, of which the subunit is encoded by the ABCC8 gene. Genetic instruments from the gene region encoding the drug target protein can proxy the antidiabetic drug of interest. Combining variant-glucose and variant-seropositive RA associations, the effect of the antidiabetic drug on RA risk is estimated by the Wald ratio test or the inverse-variance weighted method. MR estimates are scaled to RA risk per 0.1 mmol/L glucose lowering