Multiple sclerosis as a genetic risk factor for Alzheimer's disease: Insights from Mendelian randomisation
Jai Kumar Rajavoor Muniswamy1, Amrutha Reshi1, Dibyendu Roy Chowdhury2
1Rajiv Gandhi University of Health Sciences, Banglore, India.
Background:
Inflammation is implicated in neurodegeneration, but the causal link between multiple sclerosis and Alzheimer's disease remains unclear.
Objective:
To investigate the genetic relationship between MS and AD using Mendelian Randomization and assess downstream molecular effects.
Methods:
Two-sample MR was conducted using GWAS summary statistics, with IVW and MR Egger methods. Sensitivity analyses assessed pleiotropy and heterogeneity. eQTL and KEGG pathway analyses explored gene expression and functional relevance.
Results:
Sixty-four SNPs from European MS GWAS were selected for MR analysis; an African American dataset showed no significant SNPs. IVW and MR-Egger indicated a positive causal association between MS and AD (p < 0.05). Pleiotropy (Egger β = -0.017, p = 0.002) was addressed using robust methods. eQTL analysis identified 41 genes, with KEGG enrichment implicating Th1/Th2 and Th17 differentiation pathways.
Conclusion:
MS may increase AD risk via shared T-cell - mediated immunogenetic mechanisms.
Insights
Multiple sclerosis (MS) may increase Alzheimer's disease (AD) risk. This genetic study suggests shared T-cell immune pathways link these neurodegenerative conditions.
Area of Science:
- Neuroimmunology
- Genetics
- Neurodegenerative Diseases
Background:
- Inflammation plays a role in neurodegeneration.
- The causal relationship between multiple sclerosis (MS) and Alzheimer's disease (AD) is not fully understood.
Purpose of the Study:
- To investigate the genetic link between MS and AD.
- To assess downstream molecular effects using Mendelian Randomization (MR).
Main Methods:
- Two-sample MR analysis using genome-wide association study (GWAS) summary statistics.
- Inverse Variance Weighted (IVW) and MR Egger methods were employed.
- Sensitivity analyses, eQTL, and KEGG pathway analyses were conducted.
Main Results:
- A positive causal association was found between MS and AD (p < 0.05) in European datasets.
- Pleiotropy was assessed and addressed using robust statistical methods.
- eQTL analysis identified 41 genes, with KEGG enrichment pointing to T-cell differentiation pathways.
Conclusions:
- MS may elevate the risk of developing AD.
- Shared T-cell mediated immunogenetic mechanisms could underlie the link between MS and AD.
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