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

Antje K Grotz, Elena Navarro-Guerrero, Romina J Bevacqua, Roberta Baronio, Soren K Thomsen, Sameena Nawaz, Varsha Rajesh, Agata Wesolowska-Andersen, Seung K Kim, Daniel Ebner, Anna L Gloyn.
bioRxiv. 2021-05-28;
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: integration 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.
Consortium data used in this publication
Fastq sequencing files from the CRISPR screen have been deposited in the European Nucleotide Archive (ENA) at EMBL-EBI. The accession number will be made available upon publication.