The study uses a two-sample bidirectional Mendelian Randomization (MR) approach to investigate the bidirectional causal relationships between WMH phenotypes (including WMH volume, FA, and MD) and cognitive abilities (such as cognitive performance, intelligence, and cognitive function).
ABSTRACT
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.