A genome-wide CRISPR screen identifies regulators of beta cell function involved in type 2 diabetes risk [article]

Antje K Grotz, Elena Navarro-Guerrero, Romina J Bevacqua, Roberta Baronio, Soren K Thomsen, Sameena Nawaaz, Varsah Rajesh, Agata Wesolowska-Andersen, Seung K Kem, Daniel Ebner, Anna L Gloyn
2021 bioRxiv   pre-print
Identification of the genes and processes mediating genetic association signals for complex disease represents a major challenge. Since many of the genetic signals for type 2 diabetes exert their effects through pancreatic islet-cell dysfunction, we performed a genome-wide pooled CRISPR loss-of-function screen in human pancreatic beta cells. We focused on the regulation of insulin content as a disease-relevant readout of beta cell function. We identified 580 genes influencing this phenotype:
more » ... egration with genetic and genomic data provided experimental support for 20 candidate type 2 diabetes effector transcripts including the autophagy receptor CALCOCO2. Our study highlights how cellular screens can augment existing multi-omic efforts to accelerate biological and translational inference at GWAS loci.
doi:10.1101/2021.05.28.445984 fatcat:s2i7u3ooczem5mjxln5trevrh4