Systematic Functional Characterization of Candidate Causal Genes for Type 2 Diabetes Risk Variants.

ABSTRACT: Most genetic association signals for type 2 diabetes risk are located in noncoding regions of the genome, hindering translation into molecular mechanisms. Physiological studies have shown a majority of disease-associated variants to exert their effects through pancreatic islet dysfunction. Systematically characterizing the role of regional transcripts in β-cell function could identify the underlying disease-causing genes, but large-scale studies in human cellular models have previously been impractical. We developed a robust and scalable strategy based on arrayed gene silencing in the human β-cell line EndoC-βH1. In a screen of 300 positional candidates selected from 75 type 2 diabetes regions, each gene was assayed for effects on multiple disease-relevant phenotypes, including insulin sec

SUBMITTER: Thomsen SK 

PROVIDER: S-EPMC5402869 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature