Causal modeling of gene effects from regulators to programs to traits: integration of genetic associations and Perturb-seq.

ABSTRACT: Genetic association studies provide a unique tool for identifying causal links from genes to human traits and diseases. However, it is challenging to determine the biological mechanisms underlying most associations, and we lack genome-scale approaches for inferring causal mechanistic pathways from genes to cellular functions to traits. Here we propose new approaches to bridge this gap by combining quantitative estimates of gene-trait relationships from loss-of-function burden tests with gene-regulatory connections inferred from Perturb-seq experiments in relevant cell types. By combining these two forms of data, we aim to build causal graphs in which the directional associations of genes with a trait can be explained by their regulatory effects on biological programs or direct effects on t

SUBMITTER: Ota M 

PROVIDER: S-EPMC11785173 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature