Comprehensive gene heritability estimation reveals the genetic architecture of rare coding variants underlying complex traits.

ABSTRACT: Whole-exome sequencing (WES) enables high-resolution interrogation of the contribution of rare coding variants to complex trait variation. However, existing methods for heritability estimation attributed to rare-coding variants are often limited by the effects of linkage disequilibrium (LD) and by the sparse nature of rare variant data. We introduce FLEX (Fast, LD-aware Estimation of eXome-wide and gene-level heritability), a scalable and flexible framework for estimating and partitioning heritability across genes or sets of genes using WES data. FLEX integrates all coding variants- from common to ultra-rare - within a unified model and corrects for LD-induced effects to improve the accuracy of heritability estimates. In addition, FLEX supports both individual-level and summary stat

SUBMITTER: Liu Z 

PROVIDER: S-EPMC12632619 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature