LoF variant burden

Gene-based burden test results of loss of function variants (LoFs).

Variant Selection

Loss of function (LoF) variants were generated from vcf files with VEP (https://github.com/Ensembl/ensembl-vep). LoF variants are defined as having consequences in the list [frameshift_variant,splice_donor_variant,stop_gained,splice_acceptor_variant]. Also, a max_maf (0.01) and minimum info score (0.8) filters are applied. This left us with 579 genes with 2+ LoF variants that can be used for the association tests.

Endpoint

We used 2,405 binary phenotypes in the analyses.

Null Models

We used as inputs the nulls already calculated for GWAS

Association tests

Tests are performed with regenie --step2 in burden mode using a max mask (i.e. using the maximum number of ALT alleles across sites)