Year: 2020
Type: article
Abstract: The majority of genetic variants associated with type 2 diabetes (T2D) are located outside of genes in noncoding regions that may regulate gene expression in disease-relevant tissues, like pancreatic islets. Here, we present the largest integrated analysis to date of high-resolution, high-throughput human islet molecular profiling data to characterize the genome (DNA), epigenome (DNA packaging), and transcriptome (gene expression). We find that T2D genetic variants are enriched in regions of the genome where transcription Regulatory Factor X (RFX) is predicted to bind in an islet-specific manner. Genetic variants that increase T2D risk are predicted to disrupt RFX binding, providing a molecular mechanism to explain how the genome can influence the epigenome, modulating gene expression and ultimately T2D risk.
DOI: 10.17615/9kpa-wj31
Authors: Kirilusha, Anthony, Cannon, Maren E., Narisu, Narisu, Scott, Laura J., Orchard, Peter, Albanus, Ricardo D'O., Varshney, Arushi, Taylor, D. Leland, Erdos, Michael R., Chines, Peter S., Bonnycastle, Lori L., Stitzel, Michael L., Hensley, John, Kursawe, Romy, Parker, Stephen C. J., Didion, John P., Wolford, Brooke N., Welch, Ryan P., Vadlamudi, Swarooparani, Mohlke, Karen L., Collins, Francis S., Watanabe, Richard, Boehnke, Michael
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4299916091