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Causal relationship between multiple sclerosis and cortical structure: a Mendelian randomization study.

Dongren Sun1, Rui Wang1, Qin Du1

  • 1Department of Neurology, West China Hospital, Sichuan University, Guo Xuexiang #37, Chengdu, 610041, China.

Journal of Translational Medicine
|January 20, 2024
PubMed
Summary
This summary is machine-generated.

This study used Mendelian randomization to investigate the causal link between multiple sclerosis (MS) and brain structure. Findings suggest a causal relationship, with immune and inflammation pathways potentially driving cortical changes in MS patients.

Keywords:
Cortical structureMendelian randomizationMultiple sclerosis

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Area of Science:

  • Neuroscience
  • Genetics
  • Epidemiology

Background:

  • Observational studies indicate a link between multiple sclerosis (MS) and cortical structure, but findings are inconsistent.
  • Previous research has not definitively established a causal relationship between MS and alterations in brain morphology.

Purpose of the Study:

  • To employ two-sample Mendelian randomization (MR) to determine if multiple sclerosis (MS) causally influences cortical structure.
  • To identify specific cortical regions and pathways affected by MS through genetic analysis.

Main Methods:

  • Utilized large-scale genome-wide association study (GWAS) data for MS (14,498 cases, 24,091 controls) and cortical surface area/thickness (51,665 individuals).
  • Applied the inverse-variance weighted (IVW) method for primary MR analysis, with sensitivity analyses to assess heterogeneity and pleiotropy.
  • Conducted enrichment analysis on MR results to identify biological pathways involved in the MS-cortical structure relationship.

Main Results:

  • Six significant causal relationships were identified between MS and specific cortical structures, including lingual surface area, parahippocampal surface area, rostral middle frontal surface area, cuneus thickness, and lateral orbitofrontal thickness/surface area.
  • Enrichment analysis implicated leukocyte cell-related pathways, JAK-STAT signaling, NF-kappa B signaling, cytokine-cytokine receptor interaction, and prolactin signaling in MS-related cortical changes.

Conclusions:

  • This MR study provides genetic evidence supporting a causal link between multiple sclerosis (MS) and cortical structure.
  • The findings suggest that immune and inflammation-related pathways are key mediators of brain morphology abnormalities observed in MS.