ABSTRACT While emerging observational evidence suggests associations between dietary factors and cerebral small vessel disease (CSVD), the causal nature of these relationships remains unestablished. This study employed a two‐sample Mendelian randomization (MR) framework to investigate genetically predicted causal effects of dietary patterns on neuroimaging markers of CSVD. We utilized Genome‐Wide Association Study (GWAS) summary statistics from European‐ancestry cohorts for 32 dietary exposures and four CSVD phenotypes: white matter hyperintensities (WMH), lacunar strokes (LS), enlarged perivascular spaces (PVS), and brain microbleeds (BMB). Specifically, WMH volume, fractional anisotropy (FA), and mean diffusivity (MD) are indicators related to WMH. Genetic instruments (single‐nucleotide polymorphisms, SNPs) were rigorously selected using genome‐wide significance thresholds (p 0. 05). All significant findings showed no evidence of heterogeneity (PS _ heterogeneity > 0. 05) or horizontal pleiotropy (PS _ pleiotropy > 0. 05). Reverse MR analyses revealed no causal effects of CSVD features on dietary exposures (PS > 0. 05). This study provides novel genetic evidence supporting heterogeneous causal effects of dietary patterns on distinct CSVD phenotypes. The protective effect of PUFA against white matter injury, together with the beneficial role of MUFA in brain microbleeds, contrasted with iron's detrimental impact on brain microbleeds, underscoring the pathophysiological complexity of diet‐CSVD interactions. While nominally significant associations between coffee/fish intake and PVS require further validation, our findings emphasize the potential of targeted nutritional interventions in CSVD prevention. Future prospective studies with standardized dietary assessments and longitudinal neuroimaging are warranted to translate these genetic insights into clinical practice.
Zeng et al. (Sun,) studied this question.