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

IF 3.4 3区医学 Q2 CLINICAL NEUROLOGY Parkinsonism & related disorders Pub Date : 2026-01-01 Epub Date: 2025-01-31 DOI:10.1016/j.parkreldis.2025.107312

Canwen Zhang , Xiaoshuang Liu , Juan Wang , Guoqing Zhou , Biao Geng , Ming Hu , Qin Tang

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Abstract

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.

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调查脂质特征与路易体痴呆之间的因果关系：一项孟德尔随机研究。

背景：脂质代谢紊乱与多种神经退行性疾病有关。然而，脂质在路易体痴呆（DLB）发病机制中的具体作用仍知之甚少。本研究旨在利用孟德尔随机化（MR）研究脂质性状与DLB风险之间的潜在因果关系。方法：我们利用综合全基因组关联研究（GWAS）的数据，采用MR分析评估179种脂质性状与DLB之间的因果关系。脂质相关GWAS包括7174名参与者，DLB相关GWAS包括2981例DLB病例和4391名健康对照。结果：磷脂酰肌醇（PI）水平升高的遗传倾向（18:1_20:4）与DLB风险升高相关。相反，遗传倾向于增加特定磷脂酰胆碱（PC）物种的水平，包括PC (O-18:1_20:4), PC （O-16:0_20:4）和PC (O-18:0_20:4)，被发现对DLB具有保护作用。敏感性分析显示，在选择的工具变量中没有异质性或水平多效性的证据。结论：我们的MR研究确定了与DLB风险潜在因果关系的特定脂质种类。PI水平升高（18:1 . 20:4）与DLB风险增加有关，而某些PC物种的较高水平被发现具有保护作用。这些发现为DLB发病机制的脂质相关机制提供了新的见解，并突出了潜在的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Parkinsonism & related disorders 医学-临床神经学

CiteScore

6.20

自引率

4.90%

发文量

292

审稿时长

39 days

期刊介绍： Parkinsonism & Related Disorders publishes the results of basic and clinical research contributing to the understanding, diagnosis and treatment of all neurodegenerative syndromes in which Parkinsonism, Essential Tremor or related movement disorders may be a feature. Regular features will include: Review Articles, Point of View articles, Full-length Articles, Short Communications, Case Reports and Letter to the Editor.