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bioRxiv · 10.1101/2021.05.28.445984

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

Grotz, A. K.·Navarro-Guerrero, E.·Bevacqua, R. J.·Baronio, R.·Thomsen, S. K.·Nawaaz, S.·Rajesh, V.·Wesolowska-Andersen, A.·Kem, S. K.·Ebner, D.·Gloyn, A. L.
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Abstract

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.

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Grotz, A. K., Navarro-Guerrero, E., Bevacqua, R. J., Baronio, R., Thomsen, S. K., Nawaaz, S., Rajesh, V., Wesolowska-Andersen, A., Kem, S. K., Ebner, D., Gloyn, A. L.. 2021-05-28. A genome-wide CRISPR screen identifies regulators of beta cell function involved in type 2 diabetes risk. https://doi.org/10.1101/2021.05.28.445984

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