zerland / lTWAS

lTWAS

Tutorial

You may run the following command:

python3 ltwas.py location_of_sumstats1 location_of_sumstats2 \
--N1 sample_size_1 \
--N2 sample_size_2 \
--bfile location_of_reference_panel \
--chr chromosome_of_the_region \
--start start_genomic_position_of_the_region\
--end end_genomic_position_of_the_region\
--h1 local_heritability_of_trait1\
--h2 local_heritability_of_trait2\
--shrinkage parameter_for_LD_matrix_shrinkage
--out location_of_results

Explanation of Command-Line Arguments

• The first two arguments denote the locations of the first and second summary statistics files. These files may be compressed using gzip, bz2, zip, xz, or not compressed at all. The program will infer the compression method if the files end with .gz, .bz2, .zip, xz, respectively. As previously mentioned, we assume that the files are in the standard format that ldsc understands.

• The N1 and N2 arguments (optional) denote the sample sizes of the summary statistics files. If they are not provided, they will be inferred from the summary statistics files.

• The bfile argument denotes the prefix of the .bed/.bim/.fam genotypic data file. Please provide only one file which contain the genomic region you are interested in. Larger sample size in reference panel can lead to better performance of the method. (such as UKBB)

• The chr argument denotes the chromosome of the region.

• The start and end denote the start and the end genomic position of the region, respectively.

• The h1 and h2 denote the expected local heritability of trait1 and trait2 corresponding to the size of the genomic region, respectively. These are used in the calculation of weights.

• The shrinkage (optional) denotes the parameter for LD matrix shrinkage. The default is zero which means no shrinkage for LD matrix estimation. When the parameter is set as 1, the shrinkage is same with the original paper. The more the value is, the more the shrinkage is applied.

• The out flag denotes the file location for the results to be outputted to.

Explanation of Output

The output will be a whitespace-delimited text file, with the rows corresponding to different annotations and the columns as such:

• rho: The estimation of local genetic covariance.
• corr: The estimation of local genetic correlation.
• h2_1: Estimated local heritability of the first trait.
• h2_2: Estimated local heritability of the second trait.
• var: The variance of the estimation of local genetic covariance.
• p: The p value of local genetic covariance.
• m: The number of SNPs involved in the estimation of local genetic covariance in the genomic region.