Capture Hi-C reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci
Open accessAbstract
Genome-wide association studies have been tremendously successful in identifying genetic variants associated with complex diseases. The majority of association signals are intergenic and evidence is accumulating that a high proportion of signals lie in enhancer regions. We use Capture Hi-C to investigate, for the first time, the interactions between associated variants for four autoimmune diseases and their functional targets in B- and T-cell lines. Here we report numerous looping interactions and provide evidence that only a minority of interactions are common to both B- and T-cell lines, suggesting interactions may be highly cell-type specific; some disease-associated SNPs do not interact with the nearest gene but with more compelling candidate genes (for example, FOXO1, AZI2) often situated several megabases away; and finally, regions associated with different autoimmune diseases interact with each other and the same promoter suggesting common autoimmune gene targets (for example, PTPRC, DEXI and ZFP36L1).
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3C-derived methods have detected multitudes of enhancer-promoter loops in many human and mouse cell types.
“These enrichment methods have detected multitudes of enhancer–promoter loops in many human and mouse cell types [243, 286–291].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [289]
The Results (Summary of identified interactions; page unavailable) report thousands of Capture Hi-C interactions in two human cell lines, including some involving promoters. The paper does not establish that these are all enhancer–promoter loops, or report detection across many human and mouse cell types; its experiments used two human cell lines. (LLM, conf=0.88)
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- Authors
- Martin, P., McGovern, A., Orozco, G., Duffus, K., Yarwood, A., Schoenfelder, S., Cooper, N. J., Barton, A., Wallace, C., Fraser, P., Worthington, J., & Eyre, S.
- Affiliations
- Manchester Academic Health Science Centre (GB)
- Babraham Institute (GB)
- University of Cambridge (GB)
- ORCID
- Venue
- Nature Communications
- Published
- 2015-11-30
- Volume
- 6
- Issue
- 1
- Pages
- 10069-10069
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4674669
- OpenAlex
- W2182733429
- Cited by
- 213
- References
- 4
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 11 · 2023: 13 · 2022: 16 · 2021: 20 · 2020: 33 · 2019: 30 · 2018: 28 · 2017: 25 · 2016: 19 · 2015: 2
- FWCI
- 10.72
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Wellcome Trust (FP7/2007–2013, AM 095684, 091157, 089989, 095684, 100140, 097820/Z11/B, 097820, 089989/Z/09/Z)
- National Institute for Health and Care Research (20385, FP7/2007–2013, MANMKBRU-2012-1)
- University of Manchester
- European Commission (241447, 2007–2013, 115142, 305549, FP7 2007-2013, FP7/2007)
- Innovative Medicines Initiative (20385, 115142, FP7/2007‐2013)
- Versus Arthritis (20385, 20571)
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0405, BBS/E/B/000C0404)
- Cambridge Institute for Medical Research, University of Cambridge (100140)
- NIHR Cambridge Biomedical Research Centre
- FP7 Health (FP7-HEALTH-F2-2012-305549, FP7/2007-2013, 2012-305549)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- Capture Hi-C, long-range chromatin interactions, enhancer looping, candidate genes, cell type specificity, B-cell lines, T cell lines, FOXO1, CD45, DEXi, ZFP36L1, disease-associated SNPs, promoter interactions
- MeSH terms
- Adolescent, Autoimmune Diseases, B-Lymphocytes, Female, Humans, Male, Promoter Regions, Genetic, T-Lymphocytes, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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