Causal Relationship Between Ferritin and Neuropsychiatric Disorders: A Two-Sample Mendelian Randomization Study

Abstract

Background: Previous observational research has indicated a correlation between ferritin levels and neuropsychiatric disorders, although the causal relationship remains uncertain. Objective: The objective of this study was to investigate the potential causal link between plasma ferritin levels and neuropsychiatric disorders. Methods: A two-sample Mendelian randomization (MR) study was conducted, wherein genetic instruments associated with ferritin were obtained from a previously published genome-wide association study (GWAS). Summary statistics pertaining to neuropsychiatric disorders were derived from five distinct GWAS datasets. The primary MR analysis employed the inverse variance weighted (IVW) method and was corroborated by additional methods including MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses were employed to identify potential pleiotropy and heterogeneity in the results. Results: The fixed effects IVW method revealed a statistically significant causal relationship between plasma ferritin level and the occurrence of Alzheimer’s disease (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.00–1.12, p = 0.037), as well as Parkinson’s disease (OR = 1.06, 95% CI: 1.00–1.13, p = 0.041). Various sensitivity analyses were conducted, which demonstrated no substantial heterogeneity or pleiotropy. Conversely, no compelling evidence was found to support a causal association between ferritin and amyotrophic lateral sclerosis, schizophrenia, or major depressive disorder. Conclusions: This MR study provides evidence at the genetic level for a causal relationship between plasma ferritin and an increased risk of Alzheimer’s disease and Parkinson’s disease. The exact genetic mechanisms underlying this connection necessitate further investigation.