Genetic evidence of the causal relationship between serum micronutrients and Graves' disease: A Mendelian randomization and cross-sectional observational study.

Background and objectives: Exploring the effects of circulating micronutrients on Graves' disease (GD) through observational research or randomized controlled trials has drawn more attention. In order to investigate the putative causal inference, we provide an illustrative estimate of two-sample Mendelian randomization (MR) study.

Methods and study design: Inverse-variance weighted (IVW) method was employed as the primary approach to determine the causal relationships between micronutrients level and GD. Several complementary sensitivity analyses were also undertaken to evaluate the impact of potential violations of MR assumptions. In addition, we utilized cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) to analyze the differences in the prevalence of GD among participants with different levels of trace nutrient concentrations.

Results: In terms of vitamins, IVW MR analysis revealed a suggestive relationship between each standard deviation decrease in vitamin D level and increased risk of GD (OR=1.28, 95% CI: 1.04-1.59, p = 0.0212). A nominally significant association was also noted for genetically predicted vitamin B-6 concentration and higher risk of GD (OR=1.56, 95% CI: 1.08-2.25, p = 0.0171). Genetically predicted concentrations of other vitamins level and 6 minerals levels were not in association with GD susceptibility. The causal estimates from other complementary MR approaches were consistent with these findings. Additionally, we found that participants from NHANES with vitamin D and vitamin B-6 deficiency had a higher prevalence of GD.

Conclusions: Our study provides an obvious unidirectional causality of circulating vitamin B-6 and vitamin D with GD. Dietary supplementation with micronutrients may be a complement to classical therapies for preventing and treating GD.