Causal modelling of gene effects from regulators to programs to traits.

ABSTRACT: Genetic association studies provide a unique tool for identifying candidate 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 approaches to bridge this gap by combining quantitative estimates of gene-trait relationships from loss-of-function burden tests¹ with gene-regulatory connections inferred from Perturb-seq experiments² 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 p

SUBMITTER: Ota M 

PROVIDER: S-EPMC12893915 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature