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Published on: September 15, 2017
Genetically predicted plasma metabolites mediate the relation between inflammatory factors and Meniere's disease
Jian Wang1, Jian-Dao Hu1, Jing Qian1
1The Affiliated People's Hospital of Ningbo University, Department of Otorhinolaryngology Head and Neck Surgery, Zhejiang Province, China.
Objective:
Emerging evidence suggests inflammation contributes to Meniere's Disease (MD), a chronic vestibular disorder characterized by vertigo, hearing loss, and tinnitus. However, the causal role of Inflammatory Factors (IFs) and the mediating effects of Plasma Metabolites (PMs) in MD remain unclear. This study investigated bidirectional causality between IFs and MD and evaluated PMs as potential mediators.
Methods:
Using Genome-Wide Association Study (GWAS) summary data, we performed bidirectional Mendelian Randomization (MR) analyses to assess causal links between 91 IFs, 1,400 PMs, and MD. Single Nucleotide Polymorphisms (SNPs) genome-wide significant for IFs, PMs, and MD served as instrumental variables. Inverse Variance Weighting (IVW), MR-Egger, and weighted median methods were applied. Mediation analysis quantified PMs' role in IF-MD associations. Sensitivity analyses (MR-PRESSO, leave-one-out) tested robustness.
Results:
Genetically predicted higher CCL23 levels reduced MD risk (IVW OR = 0.5757 per SD decrease; 95% CI 0.3679-0.9007; p = 0.0156). No reverse causality from MD to IFs was observed (IVW OR = 0.9919; 95% CI 0.9812-1.0028; p = 0.1448). Mediation analysis revealed PMs accounted for 14.6% of the protective effect of IFs on MD. Elevated IF levels correlated with increased PMs (IVW OR = 1.0788; 95% CI 1.0125-1.1494; p = 0.0192), while higher PMs reduced MD risk (IVW OR = 0.5444; 95% CI 0.3006-0.9859; p = 0.0448). Sensitivity analyses confirmed result consistency, with no significant pleiotropy.
Conclusion:
This study identifies CCL23 as a protective factor against MD, partially mediated by PMs. Findings underscore inflammation and metabolic pathways as potential therapeutic targets. Further validation in diverse populations and exploration of biological mechanisms are needed to advance MD treatment strategies.
Insights
Inflammation may play a role in Meniere
Area of Science:
- Genetics and Epidemiology
- Immunology
- Metabolomics
Background:
- Meniere's Disease (MD) is a chronic vestibular disorder linked to inflammation.
- The precise role of inflammatory factors (IFs) and plasma metabolites (PMs) in MD pathogenesis is not fully understood.
- Investigating bidirectional causality and mediation is crucial for understanding MD development.
Purpose of the Study:
- To examine the causal relationship between 91 inflammatory factors (IFs) and Meniere's Disease (MD).
- To investigate the potential mediating role of 1,400 plasma metabolites (PMs) in the IF-MD association.
- To assess bidirectional causality using Mendelian Randomization (MR).
Main Methods:
- Genome-Wide Association Study (GWAS) summary data were utilized for bidirectional Mendelian Randomization (MR).
- Inverse Variance Weighting (IVW), MR-Egger, and weighted median methods were employed for causal inference.
- Mediation and sensitivity analyses (MR-PRESSO, leave-one-out) were performed to assess robustness and mediation effects.
Main Results:
- Elevated levels of the inflammatory factor CCL23 were found to be protective against Meniere's Disease (MD).
- No significant reverse causality was observed from MD to inflammatory factors.
- Plasma metabolites (PMs) mediated 14.6% of the protective effect of IFs on MD, with higher PMs also reducing MD risk.
Conclusions:
- CCL23 is identified as a protective factor for Meniere's Disease (MD), with a partially mediated effect through plasma metabolites (PMs).
- Inflammation and metabolic pathways represent potential therapeutic targets for MD.
- Further research is needed to validate these findings in diverse populations and elucidate underlying biological mechanisms.
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