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