Screenshot

Input Data

LD Reference Data: 1000 Genomes

BridgePRS estimates SNP-specific LD in the clumping step from an population target data in PLINK binary format. By default, the main BridgePRS includes a sample LD reference panel (BRIDGEDIR/data/1000G_sample) for population super-groups AFR and EUR that is suitable for the quick start tutorial.

A folder containing the full 1000 Genomes LD reference panel for populations AFR, EUR, EAS, SAS, and AMR can be downloaded here and unzipped into BRIDGEDIR/data/1000G_ref to enable full usage of BridgePRS.

To run BridgePRS using a custom LD reference please see customization.

Target/Base Population Data:

For the target and base populations bridgePRS requires that following files be supplied on the command line or in a configuation file:

Name Command Line flag Target Default Base Default Description
Pop Name --pop None (Required) Required Target/Base Population Name
LD-Ref Pop --ld_pop Pop Name Pop Name LD Ref Pop (AFR,EUR,EAS,AMR,SAS)
Sumstats --sumstats_prefix None (Required) Required GWAS Summary Stats (Text Format)
Genotypes --genotype_prefix None (Required) Target Genotypes Individual Level Genotypes (Plink Format)
Phenotype File --phenotype_file None (Required) Target Phenotypes Individual Level Phenotypes (Text File)
Validation File --validation_file Half of Phenotype File None Individual Level Phenotypes for Validation
QC-snp List --snp_file All Snps All Snps List QCed SNP ids

Creating a Configuration File

The following command will validate the command line data and create a target configuration file 

./bridgePRS check pop -o out --pop AFR --sumstats_prefix data/pop_africa/sumstats/afr.chr  
                                       --genotype_prefix data/pop_africa/genotypes/afr_genotypes 
                                       --phenotype_file data/pop_africa/phenotypes/afr_test.dat
To create a target and base configuation file you can use the following command: 
./bridgePRS check pops -o out --pop AFR EUR --sumstats_prefix data/pop_africa/sumstats/afr.chr data/pop_europe/sumstats/eur.chr 
                                            --genotype_prefix data/pop_africa/genotypes/afr_genotypes
                                            --phenotype_file data/pop_africa/phenotypes/afr_pheno.dat

This command will create target and base configuration files that can be observed below: 

POP=AFR
LDPOP=AFR
SUMSTATS_PREFIX=$BRIDGEDIR/data/pop_africa/sumstats/afr.chr
SUMSTATS_SUFFIX=.glm.linear.gz
SNP_FILE=$BRIDGEDIR/out/save/snps.AFR.txt
GENOTYPE_PREFIX=$BRIDGEDIR/data/pop_africa/genotypes/afr_genotypes
PHENOTYPE_FILE=$BRIDGEDIR/out/save/AFR.test_phenos.dat
VALIDATION_FILE=$BRIDGEDIR/out/save/AFR.valid_phenos.dat

POP=EUR
LDPOP=EUR
SUMSTATS_PREFIX=$BRIDGEDIR/data/pop_europe/sumstats/eur.chr
SUMSTATS_SUFFIX=.glm.linear.gz
SNP_FILE=out/save/snps.EUR.txt
GENOTYPE_PREFIX=$BRIDGEDIR/data/pop_africa/genotypes/afr_genotypes
PHENOTYPE_FILE=$BRIDGEDIR/data/pop_africa/phenotypes/afr_pheno.dat

File Specifications

1) Sumstats Data

GWAS summary statistics are provided using a prefix to one or many (per chromosome) files with the --sumstats_prefix argument and the --sumstats_suffix argument when nevecessary. GWAS summary statistics must be provided as a whitespace delimited file containing the results of an association study for a given phenotype. BridgePRS has no problem reading in a gzipped base file (need to have a .gz suffix) or splitting the file by chromosome if necessary. An example of a sumstats file with default column headers is shown:

Default Headers #CHR ID REF A1 A1_FREQ OBS_CT BETA SE T_STAT P ERRCODE
Argument --ssf-snpid --ssf-ref --ssf-alt --ssf-maf --sdf-n --ssf-beta --ssf-se --ssf-p .
Data 1 rs12184325 T G 0.0257573 4853 0.820864 0.413692 1.98424 0.0472871 .
Data 1 rs4970382 C A 0.483495 4847 0.0011142 0.128347 0.00868116 0.993074 .
Data 1 rs2710890 G G 0.424387 4814 0.108094 0.132225 0.817497 0.413687 .

The --ssf arguments can be used to specify column headers for different files.

2) Genotype Files

Genotype files must be in Plink Format.

3) Phenotype Files

Phenotype files can be provided to BridgePRS using the --phenotype_files flag. This must be a tab / space delimited file and missing data must be represented by either NA or -9 (only for binary traits). The first two column of the phenotype file should be the FID and the IID, and the rest can be phenotypes/covariates:

FID IID y y.binary PC1 PC2
afr1_1 afr2_1 24.4 1 0.53 0.950
afr1_2 afr2_2 4.10 0 0.59 0.450
afr1_3 afr2_3 37.2 1 0.73 -0.13
afr1_4 afr2_4 5.40 0 0.44 -0.55

The phenotype of interest can be specified with the --phenotype flag and the covariates can be given as a comma separated list after the --covariates flag: 

```
./bridgePRS check data -o out --pop AFR --phenotype y --covariates PC1,PC2 
                       --phenotype_file data/pop_africa/phenotypes/afr_pheno.dat 
```

Warning

The column name(s) should not contain space nor comma

4) QC SNP List

To select only SNPS that have passed QC, you can include a single column text file using the --snp_file flag.