Identifying interpretable gene-biomarker associations with functionally informed kernel-based tests in 190,000 exomes.

ABSTRACT: Here we present an exome-wide rare genetic variant association study for 30 blood biomarkers in 191,971 individuals in the UK Biobank. We compare gene-based association tests for separate functional variant categories to increase interpretability and identify 193 significant gene-biomarker associations. Genes associated with biomarkers were ~ 4.5-fold enriched for conferring Mendelian disorders. In addition to performing weighted gene-based variant collapsing tests, we design and apply variant-category-specific kernel-based tests that integrate quantitative functional variant effect predictions for missense variants, splicing and the binding of RNA-binding proteins. For these tests, we present a computationally efficient combination of the likelihood-ratio and score tests that found 36% mo

SUBMITTER: Monti R 

PROVIDER: S-EPMC9464252 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature