Calculate Polygenic Risk Score on UKB

Polygenic Risk Score, UKB

• use dx command line to log in the account in UKB RAP

dx login

• run the following shell command run swiss-army-knife of UKB RAP (extract genotyping data with some SNPs)

# pull genotyping data from UKB using UKB RAP
sh 01-pull-snps-imp37.sh

• description of some files
  • codes in 01-pull-snps-imp37.sh

  # shell command lines
  imp_file_dir="/Bulk/Imputation/UKB imputation from genotype"
  data_field="ukb22828"
  rsidlist="multiDis_SNP.txt"
  genetic_data_dir="/Genetic_data/"
  
  for i in $(seq 1 1 22); do
      run_snps="bgenix -g ${data_field}_c${i}_b0_v3.bgen -incl-rsids ${rsidlist} > chr_${i}.bgen"
  
      dx run swiss-army-knife -iin="${imp_file_dir}/${data_field}_c${i}_b0_v3.bgen" \
          -iin="${imp_file_dir}/${data_field}_c${i}_b0_v3.sample" \
          -iin="${imp_file_dir}/${data_field}_c${i}_b0_v3.bgen.bgi" \
          -iin="${genetic_data_dir}/${rsidlist}" \
          -icmd="${run_snps}" --tag="SelectSNPs" --instance-type "mem2_ssd2_v2_x16" \
          --destination="${project}:${genetic_data_dir}" --brief --yes
  done

  • part text in multiDis_SNP.txt

  rs1060743
  rs1532278
  rs3865444
  rs6656401
  rs7232

• the following analysis are run in local machine
  • combine multiple bgen files

  # combine multiple bgen files
  cat-bgen -g ukb22828_chr_1.bgen -g ukb22828_chr_2.bgen -g ukb22828_chr_3.bgen \
  -g ukb22828_chr_4.bgen -g ukb22828_chr_5.bgen -g ukb22828_chr_6.bgen -g ukb22828_chr_7.bgen \
  -g ukb22828_chr_8.bgen -g ukb22828_chr_9.bgen -g ukb22828_chr_10.bgen -g ukb22828_chr_11.bgen \
  -g ukb22828_chr_12.bgen -g ukb22828_chr_13.bgen -g ukb22828_chr_14.bgen -g ukb22828_chr_15.bgen \
  -g ukb22828_chr_16.bgen -g ukb22828_chr_17.bgen -g ukb22828_chr_18.bgen -g ukb22828_chr_19.bgen \
  -g ukb22828_chr_20.bgen -g ukb22828_chr_21.bgen -g ukb22828_chr_22.bgen -og initial_chr.bgen -clobber

  • write index file (.bgen.bgi)

  # write index file .bgen.bgi
  bgenix -g initial_chr.bgen -index -clobber

  • extract SNPs for single disease (extract SNPs of multiple diseases using the above codes)

  # extract SNPs
  disease_name="J10_INFLUPNEU"
  bgenix -g initial_chr.bgen -incl-rsids snps_${disease_name}.txt > ${disease_name}.bgen

  • write index file for disease_name .bgen.bgi

  # write index file for disease_name .bgen.bgi
  bgenix -g ${disease_name}.bgen -index -clobber

  • convert to plinkformat

  # convert to plinkformat
  plink2 --bgen ${disease_name}.bgen ref-first --sample ukb22828_c1_b0_v3.sample --freq --maf 0.01 --make-pgen --sort-vars --out ${disease_name}

  • calculate prs score

  # calculate prs score {-iin pfile, score_file}
  plink2 --pfile ${disease_name} --score ${disease_name}_scorefile.txt no-mean-imputation list-variants cols=maybefid,nallele,denom,dosagesum,scoreavgs,scoresums --out ${disease_name}_prsout.txt

  • ${disease_name}_scorefile.txt (summary statistics from the disease)

  rsid effect_allele Beta
  rs146800061 G 0.362028
  rs13088725 T 0.0946831
  rs11726368 T 0.133672
  rs117066711 C 0.388579
  rs9507345 G 0.17304
  rs2248248 G 0.14556
  rs140194168 C 0.367733
  rs28655344 C 0.14604
  rs28627461 A 0.0763166
  rs34772569 C 0.243625
  rs2837113 G 0.0779496

  • part of results

  eid   IID ALLELE_CT   DENOM   NAMED_ALLELE_DOSAGE_SUM SCORE1_AVG  SCORE1_SUM
  3274335   3274335 54  54  29.886  0.0418474   2.25976
  4217650   4217650 54  54  28.941  0.0435369   2.35099
  3332919   3332919 54  54  32.314  0.0430303   2.32363
  2602284   2602284 54  54  31.773  0.0430288   2.32356
  5418540   5418540 54  54  32.965  0.0450697   2.43377
  2806429   2806429 54  54  31.004  0.0415628   2.24439
  5922336   5922336 54  54  28.98   0.041512    2.24165
  4299370   4299370 54  54  32.745  0.0441643   2.38487
  5381487   5381487 54  54  31.012  0.0411954   2.22455
  1811259   1811259 54  54  31.969  0.042009    2.26848
  4164188   4164188 54  54  35.588  0.0456951   2.46753

• Example Polygenic risk score files
  • This example file is for type 2 Diabetes as used in PMID: 31232720
  • This example files follows the format of PMID: 35251129
  • A seconf example file fro pancreatic cancer based on the file from the PGS Catalog. PGS Catalog Pancreatic cancer PRS

Source: GitHub