Integrative modeling of transmitted and de novo variants identifies novel risk genes for congenital heart disease.

ABSTRACT:

Background

Whole-exome sequencing (WES) studies have identified multiple genes enriched for de novo mutations (DNMs) in congenital heart disease (CHD) probands. However, risk gene identification based on DNMs alone remains statistically challenging due to heterogenous etiology of CHD and low mutation rate in each gene.

Methods

In this manuscript, we introduce a hierarchical Bayesian framework for gene-level association test which jointly analyzes de novo and rare transmitted variants. Through integrative modeling of multiple types of genetic variants, gene-level annotations, and reference data from large population cohorts, our method accurately characterizes the expected frequencies of both de novo and transmitted variants and shows improved statistical

SUBMITTER: Li M 

PROVIDER: S-EPMC9000521 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature