Abstract: Objective To explore the relationship between type 1 diabetes (T1DM) and thyrotoxicosis using two-sample Mendelian randomization (MR) method. Methods Based on the data from a large-scale metabolome-based genome-wide association study (GWAS), we investigated the causality between T1DM and thyrotoxicosis using inverse variance-weighted (IVW) method, MR-Egger regression, weighted Mode (WM) method and weighted median (WME) method. Single nucleotide polymorphisms (SNPs) closely related to T1DM were screened as the instrumental variables (IVs). Outlier testing was performed using MR-PRESSON to reject the outliers. Heterogeneity tests, horizontal pleiotropy and sensitivity tests were performed to evaluate the reliability and stability of the results, and F-values were calculated to assess the presence of weak IVs bias. Results There was a positive causal effect between T1DM and thyrotoxicosis in the total samples analyzed with the 4 MR methods. The ORs and 95% CIs calculated by IVW, MR-Egger regression, WM and WME methods were 1.077 (95% CI: 1.046?1.109), 1.076 (95% CI: 1.031?1.124), 1.082 (95% CI: 1.048?1.118), and 1.090 (95% CI: 1.052?1.129), respectively. The results of the heterogeneity test were P=0.127 and P=0.155, respectively, suggesting the absence of heterogeneity. Egger-intercept result was P=0.965, indicating the absence of pleiotropy. Leave-one-out analysis showed stable results. All the F values were greater than 10, indicating that there was no weak IVs bias. Conclusion T1DM is likely to increase the risk of thyrotoxicosis.

Key words: type 1 diabetes; thyrotoxicosis; Mendelian randomization