# LoF variant burden

## 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.\
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This leaves 3,747 genes that can be used for the association tests.

## Endpoint

We used all 2,473 passing core binary phenotypes in the analyses.

## Null Models

We used as inputs the nulls already calculated for [GWAS](https://finngen.gitbook.io/documentation/methods/phewas).

## 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)