Association of Vitamins and Minerals with Type 1 Diabetes Risk: A Mendelian Randomization Study.

Area of Science:

• Genetics
• Immunology
• Nutritional Science

Background:

• Observational studies suggest nutrient deficiencies impact immune responses.
• The causal relationship between micronutrients and human autoimmune diseases like type 1 diabetes (T1D) remains unclear.
• Mendelian randomization (MR) can infer causality from genetic associations.

Purpose of the Study:

• To investigate the causal effect of 17 micronutrients on type 1 diabetes (T1D) risk.
• Utilize Mendelian randomization (MR) to overcome limitations of observational data.
• Examine T1D risk across diverse ancestral populations.

Main Methods:

• Performed a two-sample Mendelian randomization (MR) analysis.
• Used genetic variants from genome-wide association studies (GWASs) for 17 micronutrients as instrumental variables.
• Analyzed T1D GWAS data from European, multi-ancestry, Latin American/Hispanic, African American/Afro-Caribbean, and East Asian populations.
• Applied inverse variance weighted (IVW) and sensitivity analyses (MR-Egger, weighted median, MR-PRESSO, Steiger test) to ensure robustness.

Main Results:

• A significant positive causal association was found between higher serum potassium levels and increased T1D risk (OR = 1.098, p = 5.5 × 10⁻¹⁸) in multi-ancestry analysis.
• Nominal associations were observed for zinc, vitamin B12, retinol, and alpha-tocopherol.
• No significant causal effects on T1D risk were detected for vitamin C, D, K1, B6, beta- and gamma-tocopherol, magnesium, iron, copper, selenium, carotene, and folate.
• The study possessed sufficient power to detect odds ratios for T1D greater than 1.065 in the multi-ancestry analysis.

Conclusions:

• Elevated serum potassium levels are causally associated with an increased risk of type 1 diabetes (T1D).
• The observed association between potassium and T1D warrants further investigation, despite limited current observational support.
• Other common micronutrients are unlikely to exert substantial causal effects on T1D risk.