> For the complete documentation index, see [llms.txt](https://finngen.gitbook.io/documentation/llms.txt). Markdown versions of documentation pages are available by appending `.md` to page URLs; this page is available as [Markdown](https://finngen.gitbook.io/documentation/methods/lof-variant-burden.md). # LoF variant burden ## Variant Selection Loss of function (LoF) variants were generated from vcf files with VEP (). LoF variants are defined as having one of the following consequences: * 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 leaves 4,793 genes on autosomal chromosomes that can be used for the association tests. ## Endpoints We used all 2,752 passing core binary phenotypes in the analyses with the exception of PD\_DEMENTIA\_EXMORE which failed to converge during the association test. ## Association tests The null models from core additive GWAS runs were used. Tests are performed with regenie --step2 in burden mode using a max mask (i.e. using the maximum number of ALT alleles across sites). Only autosomal chromosomes (1-22) were used in the analysis. --- # Agent Instructions This documentation is published with GitBook. GitBook is the documentation platform designed so that both humans and AI agents can read, navigate, and reason over technical content effectively. Learn more at gitbook.com. ## Querying This Documentation If you need additional information that is not directly available in this page, you can query the documentation dynamically by asking a question. Perform an HTTP GET request on the current page URL with the `ask` query parameter, and the optional `goal` query parameter: ``` GET https://finngen.gitbook.io/documentation/methods/lof-variant-burden.md?ask=&goal= ``` `ask` is the immediate question: it should be specific, self-contained, and written in natural language. `goal` is optional and describes the broader end goal you are ultimately trying to accomplish on behalf of the user. GitBook uses it to tailor the answer towards what is most useful for that goal. The response will contain a direct answer to the question and relevant excerpts and sources from the documentation. Use this mechanism when the answer is not explicitly present in the current page, you need clarification or additional context, or you want to retrieve related documentation sections.