mvgwas-nf

A pipeline for multi-trait genome-wide association studies (GWAS) using MANTA.

The pipeline performs the following analysis steps:

• Split genotype file
• Preprocess phenotype and covariate data
• Test for association between phenotypes and genetic variants
• Collect summary statistics

The pipeline uses Nextflow as the execution backend. Please check Nextflow documentation for more information.

Requirements

• Unix-like operating system (Linux, MacOS, etc.)
• Java 8 or later
• Docker (v1.10.0 or later) or Singularity (v2.5.0 or later)

Quickstart (~2 min)

1. Install Nextflow:

   curl -fsSL get.nextflow.io | bash
   

2. Make a test run:

   nextflow run dgarrimar/mvgwas-nf -with-docker
   

Notes: move the nextflow executable to a directory in your $PATH. Set -with-singularity to use Singularity instead of Docker.

(*) Alternatively you can clone this repository:

git clone https://github.com/dgarrimar/mvgwas-nf
cd mvgwas-nf
nextflow run mvgwas.nf -with-docker

Important: Since release 22.12.0-edge, DSL1 is not further supported in Nextflow. Until mvgwas-nf is migrated to DSL2, the pipeline should be run using an older Nextflow release. This can be done using NXF_VER before Nextflow commands, e.g. NXF_VER=22.04.0 nextflow run dgarrimar/mvgwas-nf -with-docker.

Pipeline usage

Launching the pipeline with the --help parameter shows the help message:

nextflow run mvgwas.nf --help

N E X T F L O W  ~  version 20.04.1
Launching `mvgwas.nf` [amazing_roentgen] - revision: 56125073b7

mvgwas-nf: A pipeline for multivariate Genome-Wide Association Studies
==============================================================================================
Performs multi-trait GWAS using using MANTA (https://github.com/dgarrimar/manta)

Usage:
nextflow run mvgwas.nf [options]

Parameters:
--pheno PHENOTYPES          phenotype file
--geno GENOTYPES            indexed genotype VCF file
--cov COVARIATES            covariate file
--l VARIANTS/CHUNK          variants tested per chunk (default: 10000)
--t TRANSFOMATION           phenotype transformation: none, sqrt, log (default: none)
--i INTERACTION             test for interaction with a covariate: none, <covariate> (default: none)
--ng INDIVIDUALS/GENOTYPE   minimum number of individuals per genotype group (default: 10)
--dir DIRECTORY             output directory (default: result)
--out OUTPUT                output file (default: mvgwas.tsv)

Input files and format

mvgwas-nf requires the following input files:

• Genotypes. bgzip-compressed and indexed VCF genotype file.

• Phenotypes. Tab-separated file with phenotype measurements (quantitative) for each sample (i.e. n samples x q phenotypes). The first column should contain sample IDs. Columns should be named.

• Covariates. Tab-separated file with covariate measurements (quantitative or categorical) for each sample (i.e. n samples x k covariates). The first column should contain sample IDs. Columns should be named.

Example data is available for the test run.

Pipeline results

An output text file containing the multi-trait GWAS summary statistics (default: ./result/mvgwas.tsv), with the following information:

• CHR: chromosome
• POS: position
• ID: variant ID
• REF: reference allele
• ALT: alternative allele
• F: pseudo-F statistic
• R2: fraction of variance explained by the variant
• P: P-value

The output folder and file names can be modified with the --dir and --out parameters, respectively.

Cite mvgwas-nf

If you find mvgwas-nf useful in your research please cite the related publication:

Garrido-Martín, D., Calvo, M., Reverter, F., Guigó, R. A fast non-parametric test of association for multiple traits. Genome Biol 24, 230 (2023). https://doi.org/10.1186/s13059-023-03076-8