Evidence for genetic association between Hashimoto's thyroiditis and Sjögren's syndrome: a two-sample bidirectional mendelian randomization study.

BACKGROUND

Hashimoto's thyroiditis (HT) and Sjögren's syndrome (SS) frequently co-occur clinically, implying a potential association between the two diseases. However, their genetic association remains unclarified. To investigate whether there is a genetic link between HT and SS, we performed a two-sample bidirectional Mendelian randomization (MR) analysis.

METHODS

Data for HT were obtained from the IEU Open GWAS project, consisting of 15,654 cases and 379,986 controls. Data for SS were sourced from FinnGen Release 11, with 2981 cases and 439,424 controls included. We adopted the inverse variance-weighted (IVW) method plus four complementary robust MR methods to evaluate the genetic association between HT and SS. Comprehensive sensitivity analyses were implemented to verify the robustness of the MR estimates. Furthermore, a reverse MR analysis was performed to explore the potential for reverse association.

RESULTS

After rigorous screening, seven single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) for HT, while six SNPs served as IVs for SS. Positive MR analysis revealed a statistically significant causal effect of HT on SS, with an IVW odds ratio (OR) of 1.2188 (95% confidence interval (CI): 1.0755-1.3813; P = 0.0019). This finding was further validated by the weighted median and weighted mode methods (P < 0.05). Conversely, inverse MR analysis identified a statistically significant causal effect of SS on HT, with an IVW OR of 1.2154 (95% CI: 1.1387-1.2972; P < 0.001). This result was corroborated by the weighted median, MR-Egger, weighted mode, and simple mode methods (P < 0.05). Sensitivity analysis confirmed the robustness of these findings.

CONCLUSIONS

This study identifies a bidirectional genetic association between genetically predicted HT and SS in European populations. The observed relationship is likely attributable to shared autoimmune predisposition. These results may offer a useful reference for exploring their underlying pathogenesis. Key Points • HT and SS often coexist in clinical practice; nevertheless, the exact genetic relationship between 3 them remains to be elucidated. • A two-sample bidirectional MR approach was employed to evaluate the genetic relationship between HT and SS. • Our MR study identified a bidirectional genetic association between genetically predicted HT and SS in European populations.