RT Journal Article
SR Electronic
T1 Functional dynamic genetic effects on gene regulation are specific to particular cell types and environmental conditions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.29.428868
DO 10.1101/2021.01.29.428868
A1 Anthony S Findley
A1 Alan Monziani
A1 Allison L Richards
A1 Katie Rhodes
A1 Michelle C Ward
A1 Cynthia A Kalita
A1 Adnan Alazizi
A1 Ali Pazokitoroudi
A1 Sriram Sankararaman
A1 Xiaoquan Wen
A1 David E Lanfear
A1 Roger Pique-Regi
A1 Yoav Gilad
A1 Francesca Luca
YR 2021
UL http://biorxiv.org/content/early/2021/01/31/2021.01.29.428868.abstract
AB Genetic effects on gene expression and splicing can be modulated by cellular and environmental factors; yet interactions between genotypes, cell type and treatment have not been comprehensively studied together. We used an induced pluripotent stem cell system to study multiple cell types derived from the same individuals and exposed them to a large panel of treatments. Cellular responses involved different genes and pathways for gene expression and splicing processes, and were also highly variable across cell types and treatments. For thousands of genes, we identified variable allelic expression across contexts, and characterized different types of gene-environment interactions. Many of these G×E genes are associated with complex traits. We characterized promoter functional and evolutionary features that distinguish genes with elevated allelic imbalance mean and variance. More than 47% of the genes with dynamic regulatory interactions were missed by GTEx, but we identified them using a suitable allelic imbalance study design. This indicates the importance of exploring multiple treatments to reveal previously unrecognized regulatory loci that may be important for disease.Competing Interest StatementThe authors have declared no competing interest.