Association of 206 Brain Structural Connectivity with Different Types of Strokes: A Mendelian Randomization Study

Area of Science:

• Neuroscience
• Genetics
• Epidemiology

Background:

• The relationship between brain structural connectivity (BSC) and various stroke subtypes remains largely unexplored.
• Understanding these associations is crucial for identifying stroke risk factors and developing targeted prevention strategies.

Purpose of the Study:

• To investigate the potential causal associations between specific BSC patterns and the risk of intracerebral hemorrhage (ICH) and ischemic stroke (IS), including its subtypes.
• To explore whether genetic predispositions in BSC influence stroke susceptibility.

Main Methods:

• A two-sample, bidirectional, multivariate Mendelian randomization (MR) analysis was employed.
• Genome-wide association study (GWAS) summary statistics for BSC were integrated with stroke outcome data from large consortia (FinnGen, MEGASTROKE).
• Colocalization and reverse MR analyses were performed to confirm causal links and assess potential reverse causation.

Main Results:

• Specific white matter structural connectivity (WM-SC) patterns were significantly associated with IS risk.
• Left hemisphere somatomotor network-to-LH salience/ventral attention network WM-SC showed a positive association with IS risk.
• Right hemisphere dorsal attention network (DAN)-to-thalamus WM-SC was positively associated with IS risk, while RH DAN-to-amygdala WM-SC was negatively associated.
• A specific LH somatomotor network-to-RH visual network WM-SC pattern was linked to an increased risk of large atherosclerotic stroke.

Conclusions:

• Genetic evidence suggests distinct BSC patterns are associated with ICH, IS, and stroke subtypes.
• These findings offer insights into the genetic underpinnings of stroke and may aid in risk screening and stratification for stroke patients.