Preparing the data and obtaining polygenic risk scores

Imputing the data

The VCF files were imputed using the Sanger Imputation Service. The reference consortium chosen was the 1000Genomes Phase3 dataset and the data was pre-phased and imputed using EAGLE2.

Image of the Sanger Imputation Service

Quality control

23 imputed VCF files were obtained for the autosomes and the X chromosome. The files were combined and prepared for input into Plink2.

# To combine all the VCF files
bcftools concat 1.vcf.gz 2.vcf.gz 3.vcf.gz 4.vcf.gz 5.vcf.gz 6.vcf.gz 7.vcf.gz 8.vcf.gz 9.vcf.gz 10.vcf.gz 11.vcf.gz 12.vcf.gz 13.vcf.gz 14.vcf.gz 15.vcf.gz 16.vcf.gz 17.vcf.gz 18.vcf.gz 19.vcf.gz 20.vcf.gz 21.vcf.gz 22.vcf.gz -Oz -o combined.vcf.gz

# To remove duplicate IDs
bcftools view -H combined.vcf.gz | awk '!seen[$3]++' >> output.vcf

# To compress and index the VCF file
bgzip output.vcf
tabix -p vcf output.vcf.gz

Obtaining PRS using Plink2

This data was used as target data to compute PRS using Plink. The scoring file used was PGS000785.

plink2 
--vcf output.vcf.gz 
--score /home/vsrinivasan75/ukb_prs/PGS000785.txt 
1 4 6 no-mean-imputation 
--out patient_id