Causal Effect of Coeliac Disease on Thyroid Dysfunctions: A Mendelian Randomization Study

Abstract

Abstract Background Various epidemiological reports demonstrate that celiac disease is associated with thyroid diseases, however, it remains controversial whether this association reflects causation. We aim to investigate whether there is a causal relationship between CD and hyper- / hypo-thyroidism using the two-sample Mendelian randomization (MR) analysis. Methods Genetic variants associated (P < 5×10− 8) with CD were extracted as exposure from the IEU GWAS database in UK Biobank participants, while the hyperthyroidism or hypothyroidism summary statistics were retrieved as outcomes. Inverse-variance-weighted (IVW) method was the main MR analysis to evaluate the causal effect of CD on thyroid dysfunction risk. Then, MR-Egger and weighted median method were used for sensitivity analysis. Finally, Using Comprehensive sensitivity analyses to assessed heterogeneity and to excluded outliers with horizontal pleiotropic effects. Results IVW analysis didn't show a significant association between CD and hypothyroidism (OR = 1.97, 95% CI 0.9–4.29, P = 0.09). In contrast, genetic predisposition to CD was significantly associated with increased risk of hyperthyroidism (OR = 1.65, 95% CI 1.49–1.82, P = 1.17×−21). Multiple sensitivity analyses and statistical power endorsed the robustness of our MR results. Conclusion This study provided a genetic evidence that CD accounted for an increased risk of hyperthyroidism rather than hypothyroidism. Our findings suggest that justifies broader thyroid function and thyroid-associated-antibody screenings in CD patients.