Autoimmune Thyroid Disease and Myasthenia Gravis: A study bidirectional Mendelian randomization

Abstract

Abstract Background Previous studies have suggested a potential association between AITD and MG, but the evidence is limited and controversial, and the exact causal relationship remains uncertain. Objective Therefore, we employed a Mendelian randomization (MR) analysis to investigate the causal relationship between AITD and MG. Methods To explore the interplay between AITD and MG, We conducted MR studies utilizing GWAS-based summary statistics in the European ancestry.Several techniques were used to ensure the stability of the causal effect, such as random-effect inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO. Heterogeneity was evaluated by calculating Cochran's Q value. Moreover, the presence of horizontal pleiotropy was investigated through MR-Egger regression and MR-PRESSO Results The IVW method indicates a causal relationship between both GD(OR 1.31,95%CI 1.08 to 1.60,P = 0.005) and autoimmune hypothyroidism (OR: 1.26, 95% CI: 1.08 to 1.47, P = 0.002) with MG. However, there is no association found between FT4(OR 0.88,95%CI 0.65 to 1.18,P = 0.406), TPOAb(OR: 1.34, 95% CI: 0.86 to 2.07, P = 0.186), TSH(OR: 0.97, 95% CI: 0.77 to 1.23, P = 0.846), and MG. The reverse MR analysis reveals a causal relationship between MG and GD(OR: 1.50, 95% CI: 1.14 to 1.98, P = 3.57e-3), with stable results. On the other hand, there is a significant association with autoimmune hypothyroidism(OR: 1.29, 95% CI: 1.04 to 1.59, P = 0.019), but it is considered unstable due to the influence of horizontal pleiotropy (MR PRESSO Distortion Test P < 0.001). MG has a higher prevalence of TPOAb(OR: 1.84, 95% CI: 1.39 to 2.42, P = 1.47e-5) positivity and may be linked to elevated TSH levels(Beta:0.08,95% CI:0.01 to 0.14,P = 0.011), while there is no correlation between MG and FT4(Beta:-9.03e-3,95% CI:-0.07 to 0.05,P = 0.796). Conclusion AITD patients are more susceptible to developing MG, and MG patients also have a higher incidence of GD.