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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.

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 Illumina HiSeq 2500 13
EGAD00001005202 Illumina HiSeq 2500 6
EGAD00001005203 Illumina HiSeq 2500 3
EGAD00001005204 Illumina Genome Analyzer IIx Illumina HiSeq 2500 14
EGAD00001005205 Illumina HiSeq 2500 7
EGAD00001005206 Illumina HiSeq 2500 4
EGAD00001005207 Illumina HiSeq 2500 7
EGAD00001005208 Illumina HiSeq 2500 7
EGAD00001005209 Illumina HiSeq 2500 1
EGAD00001005210 Illumina HiSeq 2500 1
Publications Citations
TIGER: The gene expression regulatory variation landscape of human pancreatic islets.
Cell Rep 37: 2021 109807
42
Inferring causal genes at type 2 diabetes GWAS loci through chromosome interactions in islet cells.
Wellcome Open Res 8: 2023 165
0