# Causeway: a pipeline for genome-wide effector gene screening with Mendelian Randomization and colocalization

**Authors:** Julia A de Amorim, João Vitor F Cavalcante, Diego Marques-Coelho, Rodrigo J S Dalmolin, Vasiliki Lagou

PMC · DOI: 10.1093/bioadv/vbaf110 · Bioinformatics Advances · 2025-05-29

## TL;DR

Causeway is a new pipeline that efficiently identifies causal genes using Mendelian Randomization and colocalization, even on low-resource computers.

## Contribution

Causeway introduces a scalable and computationally efficient pipeline for genome-wide causal gene screening.

## Key findings

- Causeway performs two-sample Mendelian Randomization using summary statistics for gene prioritization.
- The pipeline includes sensitivity and colocalization analyses to ensure robust results.
- It is designed to work efficiently on personal computers and scale to high-performance clusters.

## Abstract

The integration of quantitative trait loci and disease genome-wide association studies for pinpointing candidate causal genes is a computationally demanding task accompanied by pitfalls related to the methods used. To address these issues, we introduce Causeway, a novel Nextflow pipeline for performing summary statistics-based two sample Mendelian Randomization for causal gene prioritization. The pipeline executes sensitivity and colocalization analyses for interrogation of findings providing robust results. The tool is designed to run tasks in a computationally efficient way even in low-resource environments, such as a personal computer. Furthermore, it can scale to web servers and high-performance computing clusters.

The source code of Causeway is available at GitHub https://github.com/juliaapolonio/Causeway, while the documentation and instructions to run the vignette at https://juliaapolonio.github.io/Causeway/.

## Full-text entities

- **Genes:** NDST1 (N-deacetylase and N-sulfotransferase 1) [NCBI Gene 3340] {aka HSST, MRT46, NST1}, FUT2 (fucosyltransferase 2 (H blood group)) [NCBI Gene 2524] {aka B12QTL1, SE, SEC2, Se2, sej}, NUP210 (nucleoporin 210) [NCBI Gene 23225] {aka GP210, POM210}, IGKV5-2 (immunoglobulin kappa variable 5-2) [NCBI Gene 28907] {aka B2, IGKV52}, AOAH (acyloxyacyl hydrolase) [NCBI Gene 313], LPAR5 (lysophosphatidic acid receptor 5) [NCBI Gene 57121] {aka GPR92, GPR93, KPG_010, LPA5}
- **Diseases:** GSMR (MESH:D019292), T2D (MESH:D003924), diabetes (MESH:D003920)
- **Chemicals:** RAM (MESH:C071315), glycosaminoglycan (MESH:D006025)

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## Figures

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## References

14 references — full list in the complete paper: https://tomesphere.com/paper/PMC12161984/full.md

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Source: https://tomesphere.com/paper/PMC12161984