Association between thyroid peroxidase antibodies and rheumatoid arthritis: insights from genetic and...

Rheumatoid arthritis (RA) has long been observed to co-occur with Hashimoto's thyroiditis, a condition characterized by the presence of thyroid peroxidase antibody (TPOAb); however, the specific contribution of TPOAb to RA pathogenesis remains unclear. Therefore, we aimed to investigate the association between TPOAb and RA.

We performed a two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary data from East Asian and European population. This analysis was complemented by functional enrichment analyses and validation using cross-sectional data from 12,014 and 5,270 participants in the National Health and Nutrition Examination Survey (NHANES).

In East Asian populations, both TPOAb concentration and TPOAb positivity were significantly associated with RA (OR = 1.447, P < 0.001; OR = 1.198, P < 0.001) and seropositive RA (OR = 1.349, P < 0.001; OR = 1.166, P = 0.002). In European populations, TPOAb concentration was significantly associated with RA, seropositive RA, and seronegative RA, while TPOAb positivity was significantly associated with RA and seropositive RA (all P < 0.05), but not seronegative RA. In the NHANES III dataset, TPOAb positivity remained significantly associated with RA and seropositive RA (OR = 1.358, P = 0.045; OR = 1.95, P = 0.046). Functional annotation further revealed enrichment of genes involved in immune regulation, immune cell differentiation, and activation.

Collectively, these findings provide genetic and observational evidence supporting an association between TPOAb and RA. However, the potential role of TPOAb in rheumatoid arthritis risk prediction requires further investigation. Key Points • TPOAb were associated with rheumatoid arthritis. • The clinical value of TPOAb for rheumatoid arthritis risk prediction requires further validation.