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Capture Hi-C reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci
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 invest...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674669/ https://www.ncbi.nlm.nih.gov/pubmed/26616563 http://dx.doi.org/10.1038/ncomms10069 |
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author | Martin, Paul McGovern, Amanda Orozco, Gisela Duffus, Kate Yarwood, Annie Schoenfelder, Stefan Cooper, Nicholas J. Barton, Anne Wallace, Chris Fraser, Peter Worthington, Jane Eyre, Steve |
author_facet | Martin, Paul McGovern, Amanda Orozco, Gisela Duffus, Kate Yarwood, Annie Schoenfelder, Stefan Cooper, Nicholas J. Barton, Anne Wallace, Chris Fraser, Peter Worthington, Jane Eyre, Steve |
author_sort | Martin, Paul |
collection | PubMed |
description | 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). |
format | Online Article Text |
id | pubmed-4674669 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46746692015-12-21 Capture Hi-C reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci Martin, Paul McGovern, Amanda Orozco, Gisela Duffus, Kate Yarwood, Annie Schoenfelder, Stefan Cooper, Nicholas J. Barton, Anne Wallace, Chris Fraser, Peter Worthington, Jane Eyre, Steve Nat Commun Article 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). Nature Pub. Group 2015-11-30 /pmc/articles/PMC4674669/ /pubmed/26616563 http://dx.doi.org/10.1038/ncomms10069 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Martin, Paul McGovern, Amanda Orozco, Gisela Duffus, Kate Yarwood, Annie Schoenfelder, Stefan Cooper, Nicholas J. Barton, Anne Wallace, Chris Fraser, Peter Worthington, Jane Eyre, Steve Capture Hi-C reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci |
title | Capture Hi-C reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci |
title_full | Capture Hi-C reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci |
title_fullStr | Capture Hi-C reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci |
title_full_unstemmed | Capture Hi-C reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci |
title_short | Capture Hi-C reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci |
title_sort | capture hi-c reveals novel candidate genes and complex long-range interactions with related autoimmune risk loci |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4674669/ https://www.ncbi.nlm.nih.gov/pubmed/26616563 http://dx.doi.org/10.1038/ncomms10069 |
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