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Published online by Cambridge University Press: 18 July 2025
Previous studies have reported comorbidities of autoimmune thyroid disorders (AITD), including Hashimoto’s disease (HT) and Graves’ disease (GD), and celiac disease (CeD), as well as the possible beneficial effects of a gluten-free diet (GFD) on AITD. Nonetheless, it remains uncertain whether there is a genetic causal relationship between AITD and CeD, while the beneficial effects on a GFD are controversial. This study aim to explore the causal relationship between CeD and AITD, particularly with HT, and to determine whether a GFD is beneficial for AITD. We performed a two-sample Mendelian Randomization (MR) analysis on data from the largest meta-analysis summary statistics of AITD, CeD and GFD. Genetic instrumental variables were established by pinpointing single nucleotide polymorphisms (SNPs) that relate to corresponding factors. In assessing sensitivity and heterogeneity, we conducted examinations of MR Egger, weighted median, simple mode, weighted mode, and MR Egger intercept tests. HT was found to play a pathogenic role in increasing the risk of CeD (ORIVW = 1.544 [95%CI 1.153-2.068], p = 0.00355), and our Mendelian randomization study does not support genetic liability related to CeD with GD (Graves’ disease) and GFD with AITD. This study supports the positive correlation between HT risk and CeD risk, while GFD has no protective effect on AITD and may exert its effect through other mechanisms. These findings provide valuable insights into potential targets for disease intervention and treatment at the genetic level.