Bidirectional Mendelian randomization study of causal associations between white-matter st

206 tractography-derived white-matter structural connectivity phenotypes from 26,333 UK Biobank participants were analyzed against multiple sclerosis susceptibility data from 115,803 individuals. Zhenxing Yu published this bidirectional two-sample Mendelian randomization study on figshare in April 2026. The results support a circuit-selective model where genetically influenced variation in specific cortico-subcortical connections is associated with MS susceptibility.

Use Cases

• Conducting Mendelian randomization analyses based on GWAS summary statistics for white-matter phenotypes.
• Investigating causal links between specific brain network architectures and disease risk based on the described salience/control and default-mode/limbic circuit associations.
• Prioritizing specific white-matter connections for further neurological study based on the 12 phenotypes identified as associated with MS susceptibility.
• Assessing the absence of reverse causal effects to distinguish predisposing factors from disease consequences.

Strengths

• Uses large-scale genetic data from two sources: 26,333 individuals for connectivity phenotypes and 115,803 individuals for MS susceptibility.
• Analyzes 206 distinct white-matter structural connectivity phenotypes derived from tractography.
• Employs multiple Mendelian randomization methods (IVW, MR-Egger, weighted median, etc.) for robustness assessment.
• Results are specific, identifying 12 WMSC phenotypes and their non-random distribution across the structural connectome.

Limitations

• Row count for the underlying summary statistics data is unknown, which may limit suitability assessment.
• Column-level documentation is absent; field semantics must be inferred from the accompanying DOCX/XLSX files after download.
• Data is derived from individuals of European ancestry, which may limit generalizability to other populations.

Provenance

Source

UK Biobank (WMSC phenotypes) and IMSGC (MS susceptibility GWAS).

Collection Method

Bidirectional two-sample Mendelian randomization using genome-wide association study summary statistics.

Freshness

Last updated 2026-04-21 03:47:26.

Geography

Data from participants of European ancestry.