Bidirectional causality between micronutrients and mental illness: Mendelian randomization studies

Background: Previous observational clinical research has suggested a link between micronutrients and psychiatric conditions. However, the causal relationship between these nutrients and mental health disorders remains uncertain. This study endeavors to fill this knowledge gap by employing a Mendelian randomization (MR) analysis on pooled data from genome-wide association studies (GWAS), aiming to explore the potential causal associations between 20 prevalent micronutrients and 7 common psychiatric disorders. Methods: A collection of single nucleotide polymorphisms (SNPs) associated with 20 micronutrients and seven common psychiatric disorders and extracted from a dataset comprising 7,368,835 individuals. MR analysis, including inverse variance weighting (IVW), Mendelian randomization-egger, weighted median, and sensitivity analysis, was used to evaluate the reliability of the study results. A significance threshold of p <0.05 was used to identify evidence of potential associations. Results: Our forward MR analysis found some commonalities between certain micronutrients and psychiatric disorders. Notably, Vitamin D level is related to the risk of reducing depression and emotional disorders. Carotene levels were associated with an elevated risk of depression, mood disorders, bipolar disorder (BIPO), and post-traumatic stress disorder (PTSD). Additionally, multivitamins +/- minerals and retinol were associated with a decreased risk of BIPO, while folate and selenium levels were associated with decreased risks of dementia and schizophrenia, respectively. The study found a significant association between elevated copper levels and an increased likelihood of Bipolar Disorder (BD), while magnesium levels were observed to be positively correlated with a heightened risk of depression. Our sensitivity study confirmed the results of the IVW MR primary analysis. Conclusion: Our study suggests that carotene, copper, and magnesium are important risk factors for depression, mood disorders, PTSD, phobia, BIPO, and dementia. Elevated levels of these micronutrients are related to an increased likelihood of these disorders.