mGWAS-Explorer 2.0: Causal Analysis and Interpretation of Metabolite-Phenotype Associations

Metabolomics-based genome-wide association studies (mGWAS) are key to understanding the genetic regulations of metabolites in complex phenotypes. We previously developed mGWAS-Explorer 1.0 to link single-nucleotide polymorphisms (SNPs), metabolites, genes and phenotypes for hypothesis generation. It has become clear that identifying potential causal relationships between metabolites and phenotypes, as well as providing deep functional insights, are crucial for further downstream applications. Here, we introduce mGWAS-Explorer 2.0 to support the causal analysis between >4000 metabolites and various phenotypes. The results can be interpreted within the context of semantic triples and molecular quantitative trait loci (QTL) data. The underlying R package is released for reproducible analysis. Using two case studies, we demonstrate that mGWAS-Explorer 2.0 is able to detect potential causal relationships between arachidonic acid and Crohn's disease, as well as between glycine and coronary heart disease.

Automated summary

Metabolomics-based genome-wide association studies (mGWAS) play a crucial role in understanding the genetic regulations of metabolites in complex phenotypes. We introduce mGWAS-Explorer 2.0 to analyze the causal relationships between over 4000 metabolites and various phenotypes, using semantic triples and molecular quantitative trait loci (QTL) data. This tool allows reproducible analysis and has successfully detected potential causal relationships in two case studies.