认知能力与白质高信号表型之间的相互作用：双向因果关系的新视角。
The Interaction Between Cognitive Abilities and White Matter Hyperintensity Phenotypes: A Novel Perspective on Bidirectional Causality.
作者信息
Ren Xiaolu, Li Ting, Li Fang, Liu Shan
机构信息
Department of Radiology, General Hospital of Ningxia Medical University, Yinchuan, China.
School of Health Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
出版信息
Brain Behav. 2025 Feb;15(2):e70313. doi: 10.1002/brb3.70313.
PURPOSE
This study utilizes bidirectional Mendelian randomization (MR) to examine the causal relationships between white matter hyperintensity (WMH) phenotypes-namely, WMH volume, fractional anisotropy (FA), and mean diffusivity (MD)-and cognitive abilities, including cognitive performance, intelligence, and overall cognitive function.
METHODS
This study leverages genetic variation data from genome-wide association study (GWAS) datasets and employs a bidirectional two-sample MR analysis. The analysis incorporates MR Egger, weighted median, weighted mode, and inverse variance weighted (IVW) methods to assess the bidirectional causal relationship between cognitive abilities and WMH volume, FA, and MD.
RESULTS
This study employed MR to explore the causal relationships between WMH volume, FA, MD, and cognitive outcomes. Most MR methods yielded nonsignificant p values (>0.05) and wide confidence intervals. Heterogeneity tests indicated no significant heterogeneity or pleiotropy between WMH volume and cognitive performance or intelligence. However, significant heterogeneity was found between WMH volume and cognitive function, FA with cognitive performance and intelligence, and MD with cognitive performance and intelligence. Reverse analysis also revealed no significant causal relationships.
CONCLUSIONS
This study suggests that the bidirectional causal effects between cognitive abilities and WMH volume, FA, and MD are minimal or nonsignificant and highlights data heterogeneity as a concern.
目的
本研究采用双向孟德尔随机化（MR）方法，以检验白质高信号（WMH）表型（即WMH体积、分数各向异性（FA）和平均扩散率（MD））与认知能力之间的因果关系，认知能力包括认知表现、智力和整体认知功能。
方法
本研究利用全基因组关联研究（GWAS）数据集的基因变异数据，并采用双向双样本MR分析。该分析纳入了MR Egger、加权中位数、加权众数和逆方差加权（IVW）方法，以评估认知能力与WMH体积、FA和MD之间的双向因果关系。
结果
本研究采用MR方法探索WMH体积、FA、MD与认知结果之间的因果关系。大多数MR方法得出的p值不显著（>0.05），置信区间较宽。异质性检验表明，WMH体积与认知表现或智力之间不存在显著的异质性或多效性。然而，在WMH体积与认知功能、FA与认知表现和智力、MD与认知表现和智力之间发现了显著的异质性。反向分析也未发现显著的因果关系。
结论
本研究表明，认知能力与WMH体积、FA和MD之间的双向因果效应极小或不显著，并强调数据异质性是一个需要关注的问题。
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