#Gene Risk Score automatical turn and twists automatically from vcf file and specs ##You'll need the following:

1. A csv-file (american with ',' as seperator) (referred as SNPlist.csv) with the SNPs from the litterature you want in your GRS. NB: Has to be in the same format as example.list

   • Crucial info is:

   • Effect allele and non-effect allele

   • SNP name (rs-number)

   • N in study

     • crucial when several studies report same SNP or SNPs in high LD

   • P-value

     • used as N, but also when using a p-value cut-off for what to include in your GRS

   • Chr and position

     • used to extract genotypes from VCF-file
     • NB: chromosome and position on build 37 (same as HRC panel)

   • Effect (only for a weighted GRS)

     • measured in standard deviations (SD) from a rank-normalized transformation. Check your paper

   • Effect Allele Frequency (EAF)

• Non-crucial, but nice to have for later comparison:
  • Locus or nearest gene
  • Note for notes

2. A spec-file (referred as GRS.spec) where you specify which GRS or combinations of GRS you want.

• Again format is important - see example (only - and + is allowed, no spaces, one GRS pr. line)
  • If you don't specify a spec-file no combinations of GRS is calculated, instead you will just get one GRS for each trait in your csv-file.

3. A id-file (reffered as IDs.list) with the IDs of the individuals in your study. One individual pr. line.

• NB: Has to be exactly the same IDs as in your VCF header. Check beforehand

4. A already formatted VCF-file to the script (see example) or path to the imputed genotypes (in vcf-format and with names as 1.vcf.gz for chr1) and use script 1_create_geno_from_vcf.sh

5. A good relation with me, Vincent, if the case of trouble-shooting.

##Running the program

1. Start by running the setup:

• ./0_setup.sh path-to-impute-folder-with-vcfs

2. (Optinal) Create the formatted vcf-file for R by:

• ./1_create_geno_from_vcf.sh SNPlist.csv

• When finished (quits after submitting two scripts to the grid-engine (check with qstat -f)) two files are created in the folder: genoFile.noHead and newHeader along some gridengine outputs

3. Then run the main script with the arguments as follows. If you have created your own geno file, header and/or ld-file, then these can be specified with --geno, --head and --ldfile, repectively.

• ./2_create_GRS.R --snp SNPlist.csv --ids IDs.list --spec GRS.spec --out example --pcut 1e-7 --ldcut 0.5

  • Besides the two first arguments (--snp and --ids) everything else is optinal:

    • --spec Name of file containting specifications for how to combine GRSs. See example GRS.spec

    • --out (default='GRS.output'). Name of outputfile.

    • --pcut (default=5e-8 (GWAS significant)). Threshold for inclusion of SNPs in GRS.

    • --ldcut (default 0.8). Threshold for pruning SNPs with a R2 above cutoff.

By Vincent Appel