ExPheWas: a platform for cis-Mendelian randomization and gene-based association scans

Area of Science:

• Genetics
• Bioinformatics
• Human Genetics

Background:

• Understanding gene-phenotype relationships is crucial for disease etiology.
• Existing tools lack comprehensive gene-based phenome-wide association study (PheWAS) and Mendelian randomization capabilities.

Purpose of the Study:

• To introduce ExPheWas, a novel gene-based PheWAS browser and platform.
• To enable gene-based Mendelian randomization analyses.
• To provide interactive data exploration tools for genetic association studies.

Main Methods:

• Developed a data repository with sex-stratified and sex-combined gene-based association results for 26,616 genes and 1746 phenotypes.
• Utilized data from up to 413,133 UK Biobank participants.
• Integrated interactive visualizations, false discovery rate control, and enrichment analysis tools.
• Implemented an interactive Mendelian randomization module using single-gene instrumental variables.

Main Results:

• ExPheWas provides a comprehensive resource linking genes to phenotypes.
• The platform facilitates exploration of genetic associations across a wide range of human traits.
• Interactive Mendelian randomization allows causal inference of gene-phenotype relationships.

Conclusions:

• ExPheWas serves as a valuable resource for researchers investigating gene-phenotype associations.
• The platform enhances the study of molecular disease etiology through gene-based PheWAS and Mendelian randomization.
• ExPheWas supports the discovery of causal genetic effects on human phenotypes.