Mendelian randomization analysis reveals causal relationships between iron loading in subcortical regions and the risk of developing dementia

Motivation: Observational studies showed a relationship between iron levels in subcortical regions and cognition. However, the causal association between them remains unclear. Goal(s): To explore the causal associations between iron levels in subcortical regions and cognitive impairment. Approach: Two-sample mendelian randomization (MR) analysis was performed based on genome-wide association study (GWAS) data. Results: Meaningful IVW (primary method) results were identified, and their consistent direction was confirmed in all three methods. Most results were nominally significant. We did not detect horizontal pleiotropy. The leave-one-out test confirmed that these associations were reliable. Impact: Iron deposition in subcortical brain regions raises the risk of dementia, and subcortical susceptibility values can be used as an imaging biomarker for the clinical assessment of dementia.