Type 2 Diabetes Associated Genetic Variants Regulate Chromatin Accessibility in Human Islets.

Shubham Khetan, The Jackson Laboratory
Romy Kursawe, The Jackson Laboratory
Ahrim Youn, The Jackson Laboratory
Nathan Lawlor, The Jackson Laboratory
Alexandria Jillette, The Jackson Laboratory
Eladio J Marquez, The Jackson Laboratory
Duygu Ucar, The Jackson Laboratory
Michael L. Stitzel, The Jackson Laboratory

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.


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, 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 2949 SNPs associated with