GWAS rsID annotation and LiftOver

Summary

This repository contains workflow / scripts for:

(1) annotating GWAS with rsIDs (e.g. in regenie output, when only CHR and GENPOS columns are present)

(2) performing liftover of genome build (38 <--> 37)

Annotation and liftover can be done as a part of one workflow or completely independently.

Workflow

Please note:

• remember to make all .sh files executable (chmod 777 file.sh)
• it is recommended to do this on a server, as it might be very slow in a local environment

Obtaining genome reference data

Both data will be downloaded into refdata/ folder in the working directory (i.e. this cloned repo).

Data for rsID annotation

Download dbSNP v151 data in VCF format, and subset it to columns that are required for annotation.

To run: (recommended to run with nohup or screen as it might take a while)

./00_download_ref_data_annotation.sh 

Output: refdata/dbSNP151_refdata_build38.txt

Data for LiftOver

Download the chain files required for performing liftover; must specify the starting genome build (38 or 37).

To run:

./00_download_ref_data_liftover.sh 38 # specify build 38 or 37

Output: refdata/hg38ToHg19.over.chain or refdata/hg19ToHg38.over.chain

(1) Genome annotation

Script for performing rsID annotation; The main .sh script internally calls .R script:

├── 01_annotate_GWAS_with_rsids.sh
    └── 01_annotate_helper.R

Assumptions:

• The input GWAS file is in the regenie format (i.e. the specific column order and names; modify those in your file before running the script if needed): CHROM GENPOS ID ALLELE0 ALLELE1 A1FREQ INFO N TEST BETA SE CHISQ LOG10P EXTRA

• The input GWAS file name does not contain dots in the file name; only to separate the file extension:

  • my_GWAS.txt.gz - ok
  • my.GWAS.txt.gz - not ok

• If running on a server, make sure to load the necessary R modules: (e.g. for Exeter, uncomment line 42 in 01_annotate_GWAS_with_rsids.sh)

• The script uses the dbSNP annotation data (refdata/dbSNP151_refdata_build38.txt) generated earlier using 00_download_ref_data_annotation.sh, so it assumes that the input GWAS data is in build 38.

To run:

Provide full paths to annotaion file and input GWAS file:

./01_annotate_GWAS_with_rsids.sh /path/to/refdata/dbSNP151_refdata_build38.txt /path/to/your/GWAS.txt.gz

Output: /path/to/your/GWAS_rsids.txt.gz

(2) Genome liftover

Script for performing liftover; The main .sh script internally calls .R script:

├── 02_liftover_GWAS.sh
    └── 02_lifover_helper.R

Assumptions:

• The same assumptions as for (1) apply here;
• If running on a server, make sure you load the necessary R module: (e.g. for Exeter, uncomment line 22 in 02_liftover_GWAS.sh )

To run:

Provide full paths to input GWAS file (output from (1) or a separate file in regenie format), path to folder containing the downloaded chain files, and the starting genome build (i.e. if need b38 -> b37, add '38'):

./02_liftover_GWAS.sh /path/to/your/GWAS_rsids.txt.gz /path/to/refdata/ 38

Output: /path/to/your/GWAS_rsids_b37.txt.gz