Association of 206 brain structural connectivity with different types of strokes: a Mendelian randomization study.

The association between brain structural connectivity (BSC) and different subtypes of stroke has not been reported. The current study determined whether some BSC patterns may contribute to the risk of stroke. A two-sample, bidirectional, multivariate Mendelian randomization (MR) analysis was performed. Genome-wide aggregated data for BSC were obtained by accessing the GWAS directory of the European Bioinformatics Institute (https://www.ebi.ac.uk/gwas). Whole-brain diffusion MRI tractograms for 26,300 UK Biobank participants were reconstructed with the MRtrix3 standard pipeline followed by SIFT2 re-weighting. A co-localization analysis was performed to determine whether the association between BSC and stroke was driven by loci within genomic regions. Reverse MR was performed to evaluate potential stroke-induced changes in BSC. Left hemisphere (LH) somatomotor network-to-LH salience /ventral attention network white matter (WM) structural connectivity (SC) [OR = 1.30, P = 5.96×10^-4, P value after Bonferroni correction [P.bfr] = 0.0125] and right hemisphere (RH) dorsal attention network-to-thalamus WM-SC (OR = 1.23, P = 1.60×10^-3, P.bfr = 0.0125) were shown to have a positive association with the risk of ischemic stroke. RH dorsal attention network-to-amygdala WM-SC (OR = 0.78, P = 1.26×10^-3, P.bfr = 0.0125) showed a negative relationship with the risk of ischemic stroke. A high LH somatomotor network-to-RH visual network WM-SC (OR = 1.62, P = 9.10×10^-3, P.bfr = 0.025) was associated with an increased risk of large atherosclerotic stroke. In conclusion, the results of the current study provided some evidence from the perspective of genetics, that different BSCs may have close associations with hemorrhagic stroke, ischemic stroke, and stroke subtypes. These findings may facilitate the screening and the risk stratification for stroke patients.Significance Statement This study provided some evidence from the perspective of genetics, that the variation in structural connectivity between some brain regions may closely relate to differential risk of stroke subtypes. The findings suggest BSC can be used as an early risk marker for the screening of stoke patients. Further investigations of the underlying cerebrovascular and neurophysiologic mechanisms are still needed for the close association between structural connectivity and stoke.