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

This study assesses causal relationships between serum trace elements/nutrients and insomnia using Mendelian randomization (MR) methods. Data was collected from genome-wide association studies, single-nucleotide polymorphisms associated with serum trace elements (iron, zinc, selenium, copper, calcium, potassium, magnesium) and nutrients (carotene, folate, vitamin A, vitamin B12, vitamin B6, vitamin C, vitamin D, vitamin E) were selected as instrumental variables for a 2-sample MR analysis, using insomnia genome-wide association study summary statistics from FinnGen. The primary analysis employed the inverse variance weighted method, supplemented by MR-Egger regression (MR-Egger), weighted median (WME), simple mode, and weighted mode approaches. Causal effects were estimated using inverse variance weighted-derived P-values, odds ratios (ORs), and 95% confidence intervals (CIs). Sensitivity analyses evaluated pleiotropy (MR-Egger intercept test), heterogeneity (Cochran Q test), and robustness (leave-one-out analysis). The OR and 95% CI indicated a possible causal link between magnesium levels and insomnia risk (OR = 0.869, 95% CI = 0.763-0.990, P < .05). No significant causal associations were observed for other serum trace elements or nutrients. Horizontal pleiotropy was assessed using MR-Egger and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), with no evidence of bias (MR-Egger intercept P > .05; MR-PRESSO global test P > .05). Cochran Q test revealed no heterogeneity, and leave-one-out analysis confirmed the stability of the causal effect. These sensitivity analyses collectively support the robustness of the Mendelian randomization results. MR analysis indicated a potential association between magnesium concentration and insomnia risk. However, further research is needed to elucidate the underlying biological mechanisms and establish the clinical significance of these associations.