Specificity, length and luck drive gene rankings in association studies.

ABSTRACT: Standard genome-wide association studies (GWAS) and rare variant burden tests are essential tools for identifying trait-relevant genes¹. Although these methods are conceptually similar, by analysing association studies of 209 quantitative traits in the UK Biobank^2-4, we show 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 - the importance of a gene for the trait under study relative to its importance across all traits. We find that GWAS prioritize genes near trait-specific variants, whereas burden tests prioritize trait-specific genes. Because non-coding varian

SUBMITTER: Spence JP 

PROVIDER: S-EPMC12823407 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature