MendelR: A one-stop R toolkit for Mendelian randomization analysis

MendelR is a fully automated, comprehensive R package specifically designed to overcome the significant technical challenges inherent in Mendelian randomization studies. By integrating the latest multi-omics databases and advanced analytical methods into a unified, user-friendly platform, it provides a complete one-stop solution for researchers aiming to derive causal inferences from observational data. The toolkit democratizes robust causal inference analysis, making it accessible to a broad audience, from those new to MR to seasoned experts, thereby accelerating discovery across biomedical research.

The platform's core strength lies in its revolutionary multi-omics integration and batch analysis capabilities. It empowers researchers to move beyond examining single exposure-outcome pairs to conducting large-scale, systems-level analyses. MendelR comes equipped with an extensive built-in repository of curated data, including thousands of metabolites, proteins, immune cell traits, and gut microbiota features, alongside seamless connectivity to major functional genomics databases like eQTL and pQTL. This enables high-throughput screening of causal relationships across different biological layers. The innovative MR-PheWAS function allows for the investigation of a specific exposure's effect on thousands of phenotypes in a single, efficient analysis, providing powerful support for hypothesis generation.

A sophisticated, intelligent data processing and quality control engine automates the most labor-intensive aspects of MR analysis. This system handles data harmonization, handles missing values, performs instrumental variable selection, and conducts rigorous quality checks with minimal user input. It incorporates advanced algorithms for LD pruning, Steiger filtering for directionality, and outlier detection using MR-PRESSO and RadialMR. Furthermore, built-in false discovery rate and Bonferroni corrections ensure the reliability of findings in large-scale analyses. This comprehensive automation transforms MR from a "technology-intensive" chore into an "idea-intensive" process, allowing scientists to concentrate on interpreting results and formulating biological insights rather than managing computational details.

MendelR does not compromise depth for ease of use. It offers a complete causal inference toolkit that integrates both standard and cutting-edge methods. Researchers have access to classic approaches like Inverse-Variance Weighted and MR-Egger regression, alongside advanced techniques for pleiotropy correction such as CAUSE, and multivariate MR to untangle complex exposure relationships. Crucially, the platform strengthens causal claims by seamlessly incorporating validation methods like colocalization analysis to verify if MR results are driven by a shared causal variant, and LDSC regression for genetic correlation, providing a multi-faceted layer of confidence to the findings.

The utility of MendelR is demonstrated by its rapid adoption and successful application in over 100 high-impact studies across diverse fields such as immunology, neuroscience, and metabolic disease. It has been used to identify novel potential drug targets and elucidate complex disease mechanisms. Designed for accessibility, its intuitive functions and detailed documentation allow researchers with limited programming experience to generate publication-ready results and visualizations quickly. By significantly lowering the technical barriers to rigorous causal inference, MendelR is not just a software tool but a catalyst for a paradigm shift, empowering the research community to confidently move from observing associations to understanding causation.