Specificity, length, and luck: How genes are prioritized by rare and common variant association studies.

ABSTRACT: Standard genome-wide association studies (GWAS) and rare variant burden tests are essential tools for identifying trait-relevant genes. Although these methods are conceptually similar, we show by analyzing association studies of 209 quantitative traits in the UK Biobank that they systematically prioritize different genes. This raises the question of how genes should ideally be prioritized. We propose two prioritization criteria: 1) trait importance - how much a gene quantitatively affects a trait; and 2) trait specificity - a gene's importance for the trait under study relative to its importance across all traits. We find that GWAS prioritize genes near trait-specific variants, while burden tests prioritize trait-specific genes. Because non-coding variants can be context spec

SUBMITTER: Spence JP 

PROVIDER: S-EPMC11812597 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature