Association between rheumatoid arthritis and autoimmune thyroid disease: evidence from complementary genetic methods

Abstract

Objectives: To assess the causal association of Rheumatoid Arthritis (RA) with Autoimmune thyroid disease (AITD).

Method: Complementary genetic approaches, including genetic correlation, Mendelian randomization (MR) and colocalization analysis, were conducted to assess the potential causal association between RA and AITD using summary statistics from large-scale genome-wide association studies (GWASs). Various sensitivity analyses had been conducted to assess the robustness and the consistency of the findings.

Results: The linkage disequilibrium score regression revealed a shared genetic structure between RA and AITD, with the significant genetic correlation between RA and autoimmune hyperthyroidism and autoimmune hypothyroidism estimated to be 0.3945 (P = 2.83 × 10^-6) and 0.2771 (P = 1.04 × 10^-6) respectively. The results of MR analysis showed that RA had a positive causal relationship with autoimmune hypothyroidism and autoimmune hyperthyroidism. The odds ratio (OR) were 1.29 (95% CI, 1.17-1.42; P = 1.08 × 10^-7) and 1.47 (95% CI, 1.25-1.72; P = 1.85 × 10^-6), respectively. In reverse MR analysis, autoimmune hypothyroidism had a positive causal relationship with RA, OR was 1.51 (95% CI, 1.37-1.66; P = 1.10 × 10^-16); autoimmune hyperthyroidism had no causal relationship with RA relationship (P = 0.22). Similar results were found using different MR methods. In addition, colocalization analysis suggested that shared causal variants existed between RA and AITD.

Conclusions: Our study suggested a potentially causal effect of genetically predicted RA on autoimmune hyperthyroidism and a bidirectional causal relationship between RA and autoimmune hypothyroidism was also observed with complementary genetic approaches, which supports the importance and necessity of thyroid function screening and monitoring in RA patient management in clinical practice.

Keywords: Autoimmune thyroid disease; Colocalization; Genetic correlation; Mendelian randomization; Rheumatoid Arthritis.