Causal relations of trace elements and nutrients with insomnia: A Mendelian randomization study

Area of Science:

• Nutritional Epidemiology
• Genetic Epidemiology
• Sleep Science

Background:

• Insomnia is a prevalent sleep disorder with significant public health implications.
• Serum trace elements and nutrients play crucial roles in physiological processes, potentially influencing sleep.
• Understanding the causal links between nutrient status and insomnia is vital for developing targeted interventions.

Purpose of the Study:

• To assess the potential causal relationships between genetically predicted serum concentrations of various trace elements and nutrients and the risk of insomnia.
• To utilize Mendelian randomization (MR) to investigate these associations, minimizing confounding factors.
• To provide robust evidence regarding the role of specific nutrients in insomnia etiology.

Main Methods:

• A two-sample Mendelian randomization (MR) analysis was conducted using genome-wide association study (GWAS) data.
• Single-nucleotide polymorphisms (SNPs) associated with serum levels of iron, zinc, selenium, copper, calcium, potassium, magnesium, carotene, folate, vitamin A, B12, B6, C, D, and E were used as instrumental variables.
• Inverse variance weighted (IVW) method was the primary analysis, with MR-Egger, weighted median, and mode-based methods used for sensitivity analyses.
• Pleiotropy and heterogeneity were assessed using MR-Egger intercept, Cochran's Q test, and MR-PRESSO.

Main Results:

• A potential inverse causal association was found between genetically predicted magnesium levels and insomnia risk (OR=0.869, 95% CI=0.763-0.990, P<0.05).
• No significant causal effects were observed for other assessed trace elements or nutrients on insomnia risk.
• Sensitivity analyses, including MR-Egger, Cochran's Q, and leave-one-out analyses, indicated no significant pleiotropy or heterogeneity, supporting the robustness of the findings.

Conclusions:

• Magnesium levels may have a causal role in the risk of developing insomnia.
• Further research is warranted to explore the biological mechanisms underlying the magnesium-insomnia association.
• These findings highlight the potential importance of magnesium in sleep health, though clinical significance requires further investigation.