PTWAS Quick Start

Software requirement

The bare minimum set of software packages for running PTWAS scan, validation, and estimation procedures are

• GAMBIT: software package implementing generalized burden test using GWAS summary statistics [download]
• PTWAS_est: perl script for causal assumption validation and effect estimation [download]
• tabix: [download]

To compute PTWAS composite instrumental variables/eQTL weights for scan analysis from users’ own eQTL data, it requires additional software packages/libraries

• DAP: Bayesian multi-SNP analysis software for fine-mapping eQTLs [download]
• ptwas_builder: utility to extract information from DAP output (part of the DAP distribution): [download]
• make_GAMBIT_DB.R: R script to format GAMBIT weights file. Requires data.table library [download]

Data requirement

PTWAS scan using GWAS summary statistics (single-SNP z-scores)

• PTWAS weights files: used by PTWAS scan procedure to construct composite IVs, also known as the eQTL weights for burden test. We provide the pre-computed weights file from 49 tissues in the GTEx project. They can be downloaded from [google drive]. To construct weights file from users’ own eQTL data, follow the detailed instructions here. Note that, the corresponding index file for a PTWAS weight file created by tabix is also needed.

• GWAS summary statistics file: GWAS single-SNP z-scores should be organized in a bgzipped vcf file. The format of the file is described here. The formatted GWAS input files for 114 complex traits described in the PTWAS paper and GTEx consortium paper can be downloaded from [google drive].

• LD reference panel: consists of a set of vcf files used for computing LD information. We can not distribute the LD panels constructed from the GTEx samples because of privacy constraints. (Users want to use GTEx panel should apply from NIH dbGap.) As an alternative, we distribute the LD panel from the 1000 Genome project (phase 3 version 5).

PTWAS validation and estimation

The input data should be formatted for each gene-trait pair. The input file is in plain text format, which is explained here.

Running analysis

Running PTWAS scan

In the simplest case, run

GAMBIT --gwas gwas_input.vcf.gz --betas ptwas_weights.vcf.gz --ldref "LD_panel_dir/chr*.vcf.gz" --ldref-only

More detailed instructions and more options are described here

Running PTWAS validation and estimation

In the simplest case, run

 ptwas_est -d gene_info.txt

For more options, please refer to here