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Extensive Association of Common Disease Variants with Regulatory Sequence
Overlap between non-coding DNA regulatory sequences and common variant associations can help to identify specific cell and tissue types that are relevant for particular diseases. In a systematic manner, we analyzed variants from 94 genome-wide association studies (reporting at least 12 loci at p<...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119736/ https://www.ncbi.nlm.nih.gov/pubmed/27875544 http://dx.doi.org/10.1371/journal.pone.0165893 |
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author | Mokry, Michal Harakalova, Magdalena Asselbergs, Folkert W. de Bakker, Paul I. W. Nieuwenhuis, Edward E. S. |
author_facet | Mokry, Michal Harakalova, Magdalena Asselbergs, Folkert W. de Bakker, Paul I. W. Nieuwenhuis, Edward E. S. |
author_sort | Mokry, Michal |
collection | PubMed |
description | Overlap between non-coding DNA regulatory sequences and common variant associations can help to identify specific cell and tissue types that are relevant for particular diseases. In a systematic manner, we analyzed variants from 94 genome-wide association studies (reporting at least 12 loci at p<5x10(-8)) by projecting them onto 466 epigenetic datasets (characterizing DNase I hypersensitive sites; DHSs) derived from various adult and fetal tissue samples and cell lines including many biological replicates. We were able to confirm many expected associations, such as the involvement of specific immune cell types in immune-related diseases and tissue types in diseases that affect specific organs, for example, inflammatory bowel disease and coronary artery disease. Other notable associations include adrenal glands in coronary artery disease, the immune system in Alzheimer’s disease, and the kidney for bone marrow density. The association signals for some GWAS (for example, myopia or age at menarche) did not show a clear pattern with any of the cell or tissue types studied. In general, the identified variants from GWAS tend to be located outside coding regions. Altogether, we have performed an extensive characterization of GWAS signals in relation to cell and tissue-specific DHSs, demonstrating a key role for regulatory mechanisms in common diseases and complex traits. |
format | Online Article Text |
id | pubmed-5119736 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-51197362016-12-15 Extensive Association of Common Disease Variants with Regulatory Sequence Mokry, Michal Harakalova, Magdalena Asselbergs, Folkert W. de Bakker, Paul I. W. Nieuwenhuis, Edward E. S. PLoS One Research Article Overlap between non-coding DNA regulatory sequences and common variant associations can help to identify specific cell and tissue types that are relevant for particular diseases. In a systematic manner, we analyzed variants from 94 genome-wide association studies (reporting at least 12 loci at p<5x10(-8)) by projecting them onto 466 epigenetic datasets (characterizing DNase I hypersensitive sites; DHSs) derived from various adult and fetal tissue samples and cell lines including many biological replicates. We were able to confirm many expected associations, such as the involvement of specific immune cell types in immune-related diseases and tissue types in diseases that affect specific organs, for example, inflammatory bowel disease and coronary artery disease. Other notable associations include adrenal glands in coronary artery disease, the immune system in Alzheimer’s disease, and the kidney for bone marrow density. The association signals for some GWAS (for example, myopia or age at menarche) did not show a clear pattern with any of the cell or tissue types studied. In general, the identified variants from GWAS tend to be located outside coding regions. Altogether, we have performed an extensive characterization of GWAS signals in relation to cell and tissue-specific DHSs, demonstrating a key role for regulatory mechanisms in common diseases and complex traits. Public Library of Science 2016-11-22 /pmc/articles/PMC5119736/ /pubmed/27875544 http://dx.doi.org/10.1371/journal.pone.0165893 Text en © 2016 Mokry et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Mokry, Michal Harakalova, Magdalena Asselbergs, Folkert W. de Bakker, Paul I. W. Nieuwenhuis, Edward E. S. Extensive Association of Common Disease Variants with Regulatory Sequence |
title | Extensive Association of Common Disease Variants with Regulatory Sequence |
title_full | Extensive Association of Common Disease Variants with Regulatory Sequence |
title_fullStr | Extensive Association of Common Disease Variants with Regulatory Sequence |
title_full_unstemmed | Extensive Association of Common Disease Variants with Regulatory Sequence |
title_short | Extensive Association of Common Disease Variants with Regulatory Sequence |
title_sort | extensive association of common disease variants with regulatory sequence |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119736/ https://www.ncbi.nlm.nih.gov/pubmed/27875544 http://dx.doi.org/10.1371/journal.pone.0165893 |
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