脂肪酸与路易体痴呆之间未被发现的关联：一项双向两样本 Mendelian Randomization 研究。

Undetected Association Between Fatty Acids and Dementia with Lewy Bodies: A Bidirectional Two-Sample Mendelian Randomization Study.

机构信息

Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Jilin University, Changchun, China.

Department of Urology, The Fourth Affiliated Hospital of Soochow University Medical Center of Soochow University, Suzhou Dushu Lake Hospital, Suzhou, China.

出版信息

J Alzheimers Dis. 2024;100(3):1083-1097. doi: 10.3233/JAD-240267.

DOI:10.3233/JAD-240267

PMID:38995791

Abstract

BACKGROUND

Although observational studies indicated connections between fatty acids (FAs) and Alzheimer's disease and dementia, uncertainty persists regarding how these relationships extend to dementia with Lewy bodies (DLB).

OBJECTIVE

To explore the potential causal relationships between FAs and the development of DLB, thus clarifying these associations using genetic instruments to infer causality.

METHODS

We applied a two-sample Mendelian randomization (MR) and multivariable Mendelian randomization (MVMR) approach. Genetic data were obtained from a DLB cohort, comprising 2,591 cases and 4,027 controls of European descent. Eight FAs, including linoleic acid, docosahexaenoic acid, monounsaturated fatty acid, omega-3 fatty acid, omega-6 fatty acid, polyunsaturated fatty acid, saturated fatty acid, and total fatty acid, were procured from a comprehensive GWAS of metabolic biomarkers of UK Biobank, conducted by Nightingale Health in 2020 (met-d), involving 114,999 individuals. Our analysis included inverse-variance weighted, MR-Egger, weighted-median, simple mode, and weighted-mode MR estimates. Cochran's Q-statistics, MR-PRESSO, and MR-Egger intercept test were used to quantify the heterogeneity and horizontal pleiotropy of instrumental variables.

RESULTS

Only linoleic acid showed a significant genetic association with the risk of developing DLB in the univariate MR. The odds ratio for linoleic acid was 1.337 with a 95% confidence interval of 1.019-1.756 (pIVW = 0.036). Results from the MVMR showed that no FAs were associated with the incidence of DLB.

CONCLUSIONS

The results did not support the hypothesis that FAs could reduce the risk of developing DLB. However, elucidating the relationship between FAs and DLB risk holds potential implications for informing dietary recommendations and therapeutic approaches in DLB.

摘要

背景

尽管观察性研究表明脂肪酸（FAs）与阿尔茨海默病和痴呆之间存在关联，但对于这些关联如何扩展到路易体痴呆（DLB）仍存在不确定性。

目的

探索 FAs 与 DLB 发展之间的潜在因果关系，从而使用遗传工具推断因果关系来阐明这些关联。

方法

我们应用了两样本 Mendelian 随机化（MR）和多变量 Mendelian 随机化（MVMR）方法。遗传数据来自一个 DLB 队列，包括 2591 例欧洲裔病例和 4027 例对照。从 2020 年 Nightingale Health 对 UK Biobank 代谢生物标志物的全基因组关联研究（met-d）中获得了包括亚油酸、二十二碳六烯酸、单不饱和脂肪酸、ω-3 脂肪酸、ω-6 脂肪酸、多不饱和脂肪酸、饱和脂肪酸和总脂肪酸在内的 8 种 FAs，该研究涉及 114999 人。我们的分析包括逆方差加权、MR-Egger、加权中位数、简单模式和加权模式 MR 估计。Cochran's Q 统计量、MR-PRESSO 和 MR-Egger 截距检验用于量化工具变量的异质性和水平多效性。