Autoimmune thyroid disease and myasthenia gravis: a study bidirectional Mendelian randomization

Abstract

BackgroundPrevious studies have suggested a potential association between AITD and MG, but the evidence is limited and controversial, and the exact causal relationship remains uncertain.ObjectiveTherefore, we employed a Mendelian randomization (MR) analysis to investigate the causal relationship between AITD and MG.MethodsTo 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-PRESSOResultsThe 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).ConclusionAITD patients are more susceptible to developing MG, and MG patients also have a higher incidence of GD.

Causal relationship between immune cell phenotypes and risk of biliary tract cancer: evidence from Mendelian randomization analysis

“…The selection criteria for IV linked to immune cell phenotypes are as follows: The threshold for single nucleotide polymorphisms associated with cell phenotypes is set at a p-value less than 1×10^ −5 . Although a p -value< 5×10^ −8 is less stringent than p -value< 5×10^ −8 ( 22 , 23 ), the small quantity of SNPs meeting the < 5×10^ −8 criterion is inadequate for subsequent analyses ( 24 , 25 ). In SNP selection, those with lower Minor Allele Frequency (MAF) are filtered out from the analysis due to their potentially minor impact on immune cell phenotypes, which could increase the risk of false positives.…”