Human islet 3D chromatin maps provide insights into type 2 diabetes

The transcriptional output of each cell type is controlled by thousands of enhancers, many of which contain genetic risk variants for common diseases such as type 2 diabetes (T2D). To gain insight into how enhancer variation influences diabetes risk, we created promoter capture Hi-C maps in human pancreatic islets. This linked diabetes-associated islet enhancers with their target genes, often located hundreds of kilobases away. We identified hubs that show spatial and functional connections between enhancersand target genes related to islet function and diabetes. We demonstrate that genetic variants distributed across hub enhancers have a major impact on T2D heritability, and use this knowledge to identify individuals in whom islet regulatory variation has a prominent role in T2D risk. Our results demonstrate the importance of 3D chromatin architecture for molecular interpretation of T2D genetic association signals, and define genomic spaces that harbor a distinct component of the T2D polygenic burden.

Type: Other
Archiver: European Genome-Phenome Archive (EGA)

10 Datasets 2 Publications

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD00001005201	13 ATAC-Seq datasets of human pancreatic islets from 13 donors	Illumina HiSeq 2500	13
EGAD00001005202	6 ChIP-Seq datasets of Mediator in human pancreatic islets from 6 donors	Illumina HiSeq 2500	6
EGAD00001005203	3 ChIP-Seq datasets of Cohesin in human pancreatic islets from 3 donors	Illumina HiSeq 2500	3
EGAD00001005204	14 ChIP-Seq datasets of H3K27ac in human pancreatic islets from 14 donors, where islets were treated in high (11mM) glucose conditions. Samples IDs HI-129, HI-130, HI-131, HI-132, HI-135, HI-137 and HI-152 were also cultured in low glucose conditions.	Illumina Genome Analyzer IIx Illumina HiSeq 2500	14
EGAD00001005205	7 H3K27ac ChIP-Seq datasets from 7 donors where islets were treated in low (4mM) glucose conditions.	Illumina HiSeq 2500	7
EGAD00001005206	4 Promoter-Capture Hi-C datasets of human pancreatic islets from 4 human islet donors	Illumina HiSeq 2500	4
EGAD00001005207	7 RNA-Seq datasets in human pancreatic islets from 7 donors, where islets were treated in high (11mM) glucose conditions	Illumina HiSeq 2500	7
EGAD00001005208	7 RNA-Seq datasets in human pancreatic islets from 7 donors, where islets were using low (4mM) glucose conditions.	Illumina HiSeq 2500	7
EGAD00001005209	Input dataset of human islets. To be used in conjuction with Cohesin and Mediator ChIP-Seq datasets.	Illumina HiSeq 2500	1
EGAD00001005210	2 Circular chromosome conformation capture (4C-Seq) datasets of the human beta cell line EndoC-bh1.	Illumina HiSeq 2500	1

Publications	Citations
TIGER: The gene expression regulatory variation landscape of human pancreatic islets. Alonso L, Piron A, Morán I, Guindo-Martínez M, Bonàs-Guarch S, Atla G, Miguel-Escalada I, Royo R, Puiggròs M, Garcia-Hurtado X, Suleiman M, Marselli L, Esguerra JLS, Turatsinze JV, Torres JM, Nylander V, Chen J, Eliasson L, Defrance M, Amela R, MAGIC, Mulder H, Gloyn AL, Groop L, Marchetti P, Eizirik DL, Ferrer J, Mercader JM, Cnop M, Torrents D. Cell Rep 37: 2021 109807	41
Inferring causal genes at type 2 diabetes GWAS loci through chromosome interactions in islet cells. Torres JM, Sun H, Nylander V, Downes DJ, van de Bunt M, McCarthy MI, Hughes JR, Gloyn AL. Wellcome Open Res 8: 2023 165	0

Publications

Citations

TIGER: The gene expression regulatory variation landscape of human pancreatic islets.
Alonso L, Piron A, Morán I, Guindo-Martínez M, Bonàs-Guarch S, Atla G, Miguel-Escalada I, Royo R, Puiggròs M, Garcia-Hurtado X, Suleiman M, Marselli L, Esguerra JLS, Turatsinze JV, Torres JM, Nylander V, Chen J, Eliasson L, Defrance M, Amela R, MAGIC, Mulder H, Gloyn AL, Groop L, Marchetti P, Eizirik DL, Ferrer J, Mercader JM, Cnop M, Torrents D. Cell Rep 37: 2021 109807

Inferring causal genes at type 2 diabetes GWAS loci through chromosome interactions in islet cells.
Torres JM, Sun H, Nylander V, Downes DJ, van de Bunt M, McCarthy MI, Hughes JR, Gloyn AL. Wellcome Open Res 8: 2023 165