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RNASeq of Calcoco2 in beta and fat cell lines

Investigation of the function of Calcoco2 by knocking it down in beta and fat cell lines.

Type: Other
Archiver: European Genome-phenome Archive (EGA)

1 Dataset 1 Publication

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD50000000518	Identification of the genes and processes mediating genetic association signals for complex diseases represents a major challenge. As many of the genetic signals for type 2 diabetes (T2D) exert their effects through pancreatic islet-cell dysfunction, we performed a genome-wide pooled CRISPR loss-of-function screen in a human pancreatic beta cell line. We assessed the regulation of insulin content as a disease-relevant readout of beta cell function and identified 580 genes influencing this phenotype. Integration with genetic and genomic data provided experimental support for 20 candidate T2D effector transcripts including the autophagy receptor CALCOCO2. Loss of CALCOCO2 was associated with distorted mitochondria, less proinsulin-containing immature granules and accumulation of autophagosomes upon inhibition of late-stage autophagy. Carriers of T2D-associated variants at the CALCOCO2 locus further displayed altered insulin secretion. Our study highlights how cellular screens can augment existing multi-omic efforts to support mechanistic understanding and provide evidence for causal effects at genome-wide association studies loci.	NextSeq 500	6

Publications	Citations
A genome-wide CRISPR screen identifies CALCOCO2 as a regulator of beta cell function influencing type 2 diabetes risk. Rottner AK, Ye Y, Navarro-Guerrero E, Rajesh V, Pollner A, Bevacqua RJ, Yang J, Spigelman AF, Baronio R, Bautista A, Thomsen SK, Lyon J, Nawaz S, Smith N, Wesolowska-Andersen A, Fox JEM, Sun H, Kim SK, Ebner D, MacDonald PE, Gloyn AL. Nat Genet 55: 2023 54-65	49