mGWAS-Explorer 2.0: Causal Analysis and Interpretation of Metabolite–Phenotype Associations
Abstract
:1. Introduction
- Implemented a two-sample MR strategy to allow the investigation of causal relationships between >4000 metabolites and various phenotypes;
- Integration of semantic triples with eQTL and pQTL data to support functional annotation and mechanistic insights from MR results;
- Added a new “Joint Search” module that allows users to flexibly enter and search different molecules of interest;
- Enhanced data harmonization workflow and released the underlying mGWASR package to support reproducible analysis.
2. Materials and Methods
2.1. Knowledgebase Curation
2.2. Methods for MR Analysis
2.3. Pre-Computed Phenome-Wide MR
2.4. Semantic Triples
2.5. R Package
3. Results
3.1. Two-Sample Mendelian Randomization (2SMR)
3.2. Pre-Computed Phenome-Wide MR
3.3. Triangulating Evidence from Semantic Triples
3.4. Enabling Joint SNP/Metabolite Analysis
3.5. Improving Transparency/Reproducibility through Releasing mGWASR Package
3.6. Case Studies
3.6.1. Crohn’s Disease Case Study
3.6.2. Coronary Heart Disease Case Study
3.7. Comparison with Other Tools
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Tool Name | mGWAS-Explorer | EpiGraphDB | The Molecular Human | MR-Base | |
---|---|---|---|---|---|
2.0 | 1.0 | ||||
Data input and processing | |||||
Metabolite | √ | √ | √ | √ | √ |
SNP | √ | √ | √ | √ | − |
Gene | √ | √ | √ | √ | − |
MR exposure | √ | − | √ | − | √ |
MR outcome | √ | − | √ | − | √ |
Output | |||||
Data table | √ | √ | √ | √ | √ |
Interactive network | +++ | +++ | ++ | ++ | − |
Forest plot | √ | − | − | − | √ |
Scatter plot | √ | − | − | − | √ |
Funnel plot | √ | − | − | − | √ |
Functions and resources | |||||
Mendelian randomization | √ | − | * √ | − | √ |
Exposure (metabolite) | ** 4238 metabolic traits, 65 studies | − | 123 metabolic traits, 1 study | − | 123 metabolic traits, 1 study |
Enrichment analysis | √ | √ | − | − | − |
Pre-computed phenome-wide MR | √ | − | √ | − | − |
Semantic triples evidence | √ | − | √ | − | − |
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Chang, L.; Zhou, G.; Xia, J. mGWAS-Explorer 2.0: Causal Analysis and Interpretation of Metabolite–Phenotype Associations. Metabolites 2023, 13, 826. https://doi.org/10.3390/metabo13070826
Chang L, Zhou G, Xia J. mGWAS-Explorer 2.0: Causal Analysis and Interpretation of Metabolite–Phenotype Associations. Metabolites. 2023; 13(7):826. https://doi.org/10.3390/metabo13070826
Chicago/Turabian StyleChang, Le, Guangyan Zhou, and Jianguo Xia. 2023. "mGWAS-Explorer 2.0: Causal Analysis and Interpretation of Metabolite–Phenotype Associations" Metabolites 13, no. 7: 826. https://doi.org/10.3390/metabo13070826