Inferring causal genes at type 2 diabetes GWAS loci through chromosome interactions in islet cells
Resolving causal genes for type 2 diabetes at loci implicated by genome-wide association studies (GWAS) requires integrating functional genomic data from relevant cell types. Chromatin features in endocrine cells of the pancreatic islet are particularly informative and recent studies leveraging chromosome conformation capture (3C) with Hi-C based methods have elucidated regulatory mechanisms in human islets. However, these genome-wide approaches are less sensitive and afford lower resolution than methods that target specific loci. Methods: To gauge the extent to which targeted 3C further resolves chromatin-mediated regulatory mechanisms at GWAS loci, we generated interaction profiles at 23 loci using next-generation (NG) capture-C in a human beta cell model (EndoC-βH1) and contrasted these maps with Hi-C maps in EndoC-βH1 cells and human islets and a promoter capture Hi-C map in human islets. Results: We found improvements in assay sensitivity of up to 33-fold and resolved ~3.6X more chromatin interactions. At a subset of 18 loci with 25 co-localised GWAS and eQTL signals, NG Capture-C interactions implicated effector transcripts at five additional genetic signals relative to promoter capture Hi-C through physical contact with gene promoters. Conclusions: High resolution chromatin interaction profiles at selectively targeted loci can complement genome- and promoter-wide maps.
- 29/05/2024
- 15 samples
- DAC: EGAC00001002601
- Technology: NextSeq 500
Data Access Policy of the Datasets from the Translational Genomics of Diabetes Lab at Stanford University
DATA ACCESS AGREEMENT This agreement governs the terms on which access will be granted to the RNA sequencing data generated as part of the CALCOCO2 study. In signing this agreement, You are agreeing to be bound by the terms and conditions of access set out in this agreement. For the sake of clarity, the terms of access set out in this agreement apply both to the User and the User’s Institution (as defined below). User Institution and User are referred to within the agreement as “You” and “Your” shall be construed accordingly. Definitions: Investigators means the group of investigators based in Stanford, US and Oxford, UK which have generated the Data. Data means all and any human genetic data obtained from the Investigators. Data Subject means a person, who has been informed of the purpose for which the Data is held and has given his/her informed consent thereto. 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You understand and acknowledge that the Data is protected by copyright and other intellectual property rights, and that duplication, except as reasonably required to carry out Your research with the Data, or sale of all or part of the Data on any media is not permitted. 10. You recognise that nothing in this agreement shall operate to transfer to the User Institution any intellectual property rights relating to the Data. The User Institution has the right to develop intellectual property based on comparisons with their own data. 11. You accept that this agreement will terminate immediately upon any breach of this agreement by You and You will be required to destroy any Data held. 12. You accept that it may be necessary for the Investigators or its appointed agent to alter the terms of this agreement from time to time in order to address new concerns. 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Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.
| Study ID | Study Title | Study Type |
|---|---|---|
| EGAS00001006105 | Other |
This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.