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

Identifying the genes or effector transcripts responsible for mediating genetic association signals is a major challenge for complex disease. For type 2 diabetes, there are hundreds of independent signals exerting their effects on disease risk with many acting through pancreatic islet-cell dysfunction. We performed a genome-wide pooled CRISPR loss-of-function screen in human pancreatic beta cells to identify genes regulating insulin content. Our study highlights how cellular screens can augment existing multi-omic efforts to accelerate biological and translational inference at GWAS loci.