Scalable mixed model methods for set-based association studies on large-scale categorical data analysis and its application to exome-sequencing data in UK Biobank.

ABSTRACT: The ongoing release of large-scale sequencing data in the UK Biobank allows for the identification of associations between rare variants and complex traits. SAIGE-GENE+ is a valid approach to conducting set-based association tests for quantitative and binary traits. However, for ordinal categorical phenotypes, applying SAIGE-GENE+ with treating the trait as quantitative or binarizing the trait can cause inflated type I error rates or power loss. In this study, we propose a scalable and accurate method for rare-variant association tests, POLMM-GENE, in which we used a proportional odds logistic mixed model to characterize ordinal categorical phenotypes while adjusting for sample relatedness. POLMM-GENE fully utilizes the categorical nature of phenotypes and thus can well control type I erro

SUBMITTER: Bi W 

PROVIDER: S-EPMC10183366 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature