Investigating the causal relationships between lipid traits and dementia with lewy bodies: A mendelian randomization study.

BACKGROUND

Disruptions in lipid metabolism have been implicated in various neurodegenerative diseases. However, the specific role of lipid species in the pathogenesis of dementia with Lewy bodies (DLB) remains poorly understood. This study aims to investigate potential causal relationships between lipid traits and DLB risk using Mendelian randomization (MR).

METHODS

We employed MR analysis to assess causal associations between 179 lipid traits and DLB, utilizing data from comprehensive genome-wide association studies (GWAS). The lipid-related GWAS included 7174 participants, and the DLB-related GWAS included 2981 DLB cases and 4391 healthy controls.

RESULTS

Genetic predispositions to increased levels of phosphatidylinositol (PI) (18:1_20:4) were associated with an elevated risk of DLB. Conversely, genetic predispositions to increased levels of specific phosphatidylcholine (PC) species, including PC (O-18:1_20:4), PC (O-16:0_20:4) and PC (O-18:0_20:4), were found to be protective against DLB. Sensitivity analyses revealed no evidence of heterogeneity or horizontal pleiotropy among the selected instrumental variables.

CONCLUSIONS

Our MR study identifies specific lipid species potentially causally linked to DLB risk. Elevated levels of PI (18:1_20:4) were associated with increased DLB risk, while higher levels of certain PC species were found to be protective. These findings offer new insights into the lipid-related mechanisms underlying DLB pathogenesis and highlight potential therapeutic targets.