White-Matter Structural Connectivity and Alzheimer's Disease: A Mendelian Randomization Study

IF 2.7 3区心理学 Q2 BEHAVIORAL SCIENCES Brain and Behavior Pub Date : 2025-02-09 DOI:10.1002/brb3.70286

Siyu Liu, Daoying Geng

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Abstract

Background

Alzheimer's disease (AD) and white-matter structural connectivity have been linked in some observational studies, although it is unknown if this is a causal relationship. The purpose of this study was to examine the impact of various white-matter structural connectivity on AD via a two-sample multivariate Mendelian randomization (MR) approach.

Methods

The genome-wide association study (GWAS) of Wainberg et al. provided the summary data on white-matter structural connectivity, and Bellenguez et al.’s study provided the GWAS aggregated data for AD. MR methods included inverse variance weighted, Mendelian randomization Egger, simple mode, weighted median, and weighted mode. Heterogeneity, horizontal pleiotropy, and “leave-one-out” analysis guaranteed the robustness of causation. Finally, reverse MR analysis was conducted on the white-matter structural connectivity that showed positive results in the forward MR analysis.

Results

Among 206 white-matter structural connections, we identified 10 connections were strongly correlated with genetic susceptibility to AD. Right-hemisphere limbic network to thalamus white-matter structural connectivity and Right-hemisphere salience_ventral attention network to accumbens white-matter structural connectivity were positively correlated with the likelihood of AD, while the remaining 8 white-matter structural connections were negatively related with AD. None of the above 10 white-matter structural connections have a reverse causal relationship with AD.

Conclusion

Our MR study reveals a certain degree of association between white-matter structural connectivity and AD, which may provide support for future diagnosis and treatment of AD.

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白质结构连接与阿尔茨海默病：一项孟德尔随机研究

背景：在一些观察性研究中，阿尔茨海默病（AD）与白质结构连通性有关，尽管尚不清楚这是否是因果关系。本研究的目的是通过双样本多元孟德尔随机化（MR）方法来检查各种白质结构连通性对AD的影响。方法Wainberg等人的全基因组关联研究（GWAS）提供了白质结构连通性的汇总数据，Bellenguez等人的研究提供了AD的GWAS汇总数据。MR方法包括方差反加权、孟德尔随机化、简单模式、加权中位数和加权模式。异质性、水平多效性和“留一”分析保证了因果关系的稳健性。最后，对白质结构连通性进行反向MR分析，正向MR分析结果为阳性。结果在206个白质结构连接中，我们发现10个连接与AD的遗传易感性密切相关。右半脑边缘网络-丘脑白质结构连接和右半脑显著性-腹侧注意网络-伏隔脑白质结构连接与AD的可能性呈正相关，其余8个白质结构连接与AD的可能性负相关。上述10种白质结构连接与AD均无反向因果关系。结论本研究揭示了白质结构连通性与AD存在一定程度的相关性，为AD的诊断和治疗提供依据。

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来源期刊

Brain and Behavior BEHAVIORAL SCIENCES-NEUROSCIENCES

CiteScore

5.30

自引率

0.00%

发文量

352

审稿时长

14 weeks

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