Abstract
Background/Objectives: Previous studies suggest that nutrient deficiencies can alter immune responses in animals. However, the impact of micronutrients on autoimmune diseases like type 1 diabetes (T1D) in humans remains unclear since the described associations are based on observational data and they cannot establish causality. This study aims to examine the causal relationship between various micronutrients and T1D using Mendelian randomization (MR). Methods: We performed a two-sample MR analysis using genetic variants from genome-wide association studies (GWASs) of 17 micronutrients as instrumental variables (IVs). We analyzed T1D GWAS datasets of European (18,942 cases/520,580controls), multi-ancestry (25,717 cases/583,311 controls), Latin American/Hispanic (2295 cases/55,134 controls), African American/Afro-Caribbean (6451 cases/109,410 controls), and East Asian (1219 cases/132,032 controls) ancestries. We applied the inverse variance weighted (IVW) method in our main analysis, and additional MR estimators (MR-Egger, weighted median, weighted mode, MR-PRESSO) to address pleiotropy, and the Steiger test to test directionality in sensitivity analyses. Results: Following Bonferroni correction (p < 0.05/17), we found positive association between potassium levels and T1D risk (OR = 1.098, 95% CI [1.075, 1.122] p = 5.5 × 10(-18)) in the multi-ancestry analysis. Zinc, vitamin B12, retinol, and alpha tocopherol showed nominal associations. Vitamin C, D, K1, B6, beta- and gamma-tocopherol, magnesium, iron, copper, selenium, carotene, and folate showed no significant effects on T1D risk. For the multi-ancestry analysis, we had sufficient power to detect ORs for T1D larger than 1.065. Conclusions: Higher serum potassium levels were associated with increased T1D risk in our MR study, though supporting observational evidence is currently limited. Other micronutrients are unlikely to have large effects on T1D.