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Causal Associations between Functional/Structural Connectivity and Stroke: A Bidirectional Mendelian Randomization
Yisong Wang1, Longtao Yang1, Jun Liu1,2,3
1Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha 410011, China.
Biomedicines
|June 28, 2023
Summary
Genetic analysis reveals that altered functional and structural connectivity in brain networks causally impacts stroke risk. Lower connectivity in some networks increases stroke risk, while others show complex bidirectional relationships.
Area of Science:
- Neuroscience
- Genetics
- Epidemiology
Background:
- Disruption of brain resting-state networks (RSNs) is linked to stroke, but causality is hard to establish in epidemiological studies.
- Genetic variants offer insights into functional connectivity (FC) and structural connectivity (SC) within RSNs.
Purpose of the Study:
- To investigate the causal relationship between FC/SC within 7 RSNs and stroke risk using Mendelian randomization.
- To explore bidirectional causal effects between RSN connectivity and stroke subtypes.
Main Methods:
- Two-sample bidirectional Mendelian randomization (MR) study.
- Utilized genome-wide association study (GWAS) data for RSNs (N=24,336) and stroke data from MEGASTROKE (N=520,000).
- Analyzed FC and SC within 7 RSNs in relation to stroke and its subtypes.
Main Results:
- Lower global mean FC and limbic network FC associated with higher risk of any ischemic stroke and small vessel stroke, respectively.
- Ventral attention network FC and default mode network SC positively related to small vessel stroke and large artery stroke risk.
- Inverse MR showed stroke causally related to dorsal attention network FC and somatomotor FC.
Conclusions:
- Provides genetic evidence for contrasting causal effects of RSN FC/SC on stroke subtypes.
- Suggests a combination of injury and compensatory processes in RSNs post-stroke.
- Highlights the need for further studies to validate findings and elucidate physiological mechanisms.
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