LDAK-KVIK steps
LDAK-KVIK uses a three-step process to test SNPs and genes for association with the phenotype:
- Compute a Leave-One-Chromosome-Out (LOCO) PRS using an Elastic Net model
- Use the PRS as offset in single-SNP analysis
- Use the summary statistics of single-SNP analysis to run a gene-based association analysis LDAK-GBAT
These steps should be run consecutively; each next step is dependent on the results of the previous step.
An example run of LDAK-KVIK is as follows:
./ldak6.linux --kvik-step1 kvik --bfile data --pheno phenofile --covar covfile --max-threads 2
./ldak6.linux --kvik-step2 kvik --bfile data --pheno phenofile --covar covfile --max-threads 2
./ldak6.linux --kvik-step3 kvik --bfile data --genefile genefile --max-threads 2
An overview of the LDAK-KVIK algorithm is included in the technical details. Here, we describe the command lines used the the main input options. Note that a more extensive list of input options is included in the the data format page.
Step 1
An example command line of Step 1 in LDAK-KVIK is given by:
./ldak6.linux --kvik-step1 kvik --bfile data --pheno phenofile --covar covfile --max-threads 2
The main input options are as follows:
| Argument | Description |
|---|---|
--kvik-step1 |
Name of the output files of the step 1 |
--bfile |
Name of the .bed file to be analyzed |
--pheno |
Name of the phenotype file |
--covar |
Name of the covariate file |
--max-threads |
Integer value, specifying the number of available threads for fitting the elastic net. By default, LDAK assumes --max-threads equals 1 |
--binary |
Indicates that the analysed trait is binary |
When analysing binary traits, the user should add --binary YES to the command. All operations in Step 1 will then be based on weighted linear regression, instead of linear regression. When analysing imputed data, it is not necessary to include all SNPs in Step 1 (see Recommendations for alternative options). A more extensive list of options can be found in data format.
Step 2
An example command line of Step 2 in LDAK-KVIK is given by:
./ldak6.linux --kvik-step2 kvik --bfile data --pheno phenofile --covar covfile --max-threads 2
The main input options are as follows:
| Argument | Description |
|---|---|
--kvik-step2 |
Name of the output files of Step 2. Note that this should have the same name as Step 1. |
--bfile |
Name of the .bed file to be analyzed |
--pheno |
Name of the phenotype file |
--covar |
Name of the covariate file |
Note that the input argument of --kvik-step2 (in this case, ‘kvik’) should match the argument previously used in --kvik-step1. In case the --binary YES flag is used in Step 1, this will automatically be used in Step 2, and a saddlepoint approximation will be used for association analysis. Note that Step 2 can only be run after Step1 has been run. More options for can be found in Data Filtering.
Step 3
An example command line of Step 3 in LDAK-KVIK is given by:
./ldak6.linux --kvik-step3 kvik --bfile data --genefile <annotfile> --max-threads 2
The main input options are as follows:
| Argument | Description |
|---|---|
--kvik-step3 |
Name of the output files of Step 3. Note that this should have the same name as Step 1 and Step 2. |
--bfile |
Name of the .bed file to be analyzed |
--genefile |
Name of the gene annotation file |
Note that a gene annotation file is needed to specify the locations of the genes on the genome. The gene-based testing page includes command lines for downloading gene annotation files.