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A transcriptome-wide Mendelian randomization study to uncover tissue-dependent regulatory mechanisms across the human phenome
Developing insight into tissue-specific transcriptional mechanisms can help improve our understanding of how genetic variants exert their effects on complex traits and disease. In this study, we apply the principles of Mendelian randomization to systematically evaluate transcriptome-wide association...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954187/ https://www.ncbi.nlm.nih.gov/pubmed/31924771 http://dx.doi.org/10.1038/s41467-019-13921-9 |
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author | Richardson, Tom G. Hemani, Gibran Gaunt, Tom R. Relton, Caroline L. Davey Smith, George |
author_facet | Richardson, Tom G. Hemani, Gibran Gaunt, Tom R. Relton, Caroline L. Davey Smith, George |
author_sort | Richardson, Tom G. |
collection | PubMed |
description | Developing insight into tissue-specific transcriptional mechanisms can help improve our understanding of how genetic variants exert their effects on complex traits and disease. In this study, we apply the principles of Mendelian randomization to systematically evaluate transcriptome-wide associations between gene expression (across 48 different tissue types) and 395 complex traits. Our findings indicate that variants which influence gene expression levels in multiple tissues are more likely to influence multiple complex traits. Moreover, detailed investigations of our results highlight tissue-specific associations, drug validation opportunities, insight into the likely causal pathways for trait-associated variants and also implicate putative associations at loci yet to be implicated in disease susceptibility. Similar evaluations can be conducted at http://mrcieu.mrsoftware.org/Tissue_MR_atlas/. |
format | Online Article Text |
id | pubmed-6954187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69541872020-01-13 A transcriptome-wide Mendelian randomization study to uncover tissue-dependent regulatory mechanisms across the human phenome Richardson, Tom G. Hemani, Gibran Gaunt, Tom R. Relton, Caroline L. Davey Smith, George Nat Commun Article Developing insight into tissue-specific transcriptional mechanisms can help improve our understanding of how genetic variants exert their effects on complex traits and disease. In this study, we apply the principles of Mendelian randomization to systematically evaluate transcriptome-wide associations between gene expression (across 48 different tissue types) and 395 complex traits. Our findings indicate that variants which influence gene expression levels in multiple tissues are more likely to influence multiple complex traits. Moreover, detailed investigations of our results highlight tissue-specific associations, drug validation opportunities, insight into the likely causal pathways for trait-associated variants and also implicate putative associations at loci yet to be implicated in disease susceptibility. Similar evaluations can be conducted at http://mrcieu.mrsoftware.org/Tissue_MR_atlas/. Nature Publishing Group UK 2020-01-10 /pmc/articles/PMC6954187/ /pubmed/31924771 http://dx.doi.org/10.1038/s41467-019-13921-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Richardson, Tom G. Hemani, Gibran Gaunt, Tom R. Relton, Caroline L. Davey Smith, George A transcriptome-wide Mendelian randomization study to uncover tissue-dependent regulatory mechanisms across the human phenome |
title | A transcriptome-wide Mendelian randomization study to uncover tissue-dependent regulatory mechanisms across the human phenome |
title_full | A transcriptome-wide Mendelian randomization study to uncover tissue-dependent regulatory mechanisms across the human phenome |
title_fullStr | A transcriptome-wide Mendelian randomization study to uncover tissue-dependent regulatory mechanisms across the human phenome |
title_full_unstemmed | A transcriptome-wide Mendelian randomization study to uncover tissue-dependent regulatory mechanisms across the human phenome |
title_short | A transcriptome-wide Mendelian randomization study to uncover tissue-dependent regulatory mechanisms across the human phenome |
title_sort | transcriptome-wide mendelian randomization study to uncover tissue-dependent regulatory mechanisms across the human phenome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954187/ https://www.ncbi.nlm.nih.gov/pubmed/31924771 http://dx.doi.org/10.1038/s41467-019-13921-9 |
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