Type 2 Diabetes-Associated Genetic Variants Regulate Chromatin Accessibility in Human Islets.
Diabetes 2018 Nov; 67(11):2466-2477
Doug Coleman research Fund at The Jackson Laboratory, DK092251, ADA Pathway to Stop Diabetes Accelerator Award 1-18-ACE-15
Type 2 diabetes (T2D) is a complex disorder in which both genetic and environmental risk factors contribute to islet dysfunction and failure. Genome-wide association studies (GWAS) have linked single nucleotide polymorphisms (SNPs), most of which are noncoding, in >200 loci to islet dysfunction and T2D. Identification of the putative causal variants and their target genes and whether they lead to gain or loss of function remains challenging. Here, we profiled chromatin accessibility in pancreatic islet samples from 19 genotyped individuals and identified 2,949 SNPs associated with in vivo
Khetan, Shubham; Kursawe, Romy; Youn, Ahrim; Lawlor, Nathan; Jillette, Alexandria; Marquez, Eladio J; Ucar, Duygu; and Stitzel, Michael L., "Type 2 Diabetes-Associated Genetic Variants Regulate Chromatin Accessibility in Human Islets." (2018). Faculty Research 2018. 212.
We thank Jane Cha, Jackson Laboratory for Genomic Medicine, for help generating artwork for the figures, members of the Stitzel and Ucar labs for helpful discussion and critiques during study design and execution, and Taneli Helenius, Jackson Laboratory for Genomic Medicine, and anonymous reviewers, whose comments, questions, and suggested edits greatly improved the quality and clarity of this manuscript.