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Genome-wide identification of directed gene networks using large-scale population genomics data
Identification of causal drivers behind regulatory gene networks is crucial in understanding gene function. Here, we develop a method for the large-scale inference of gene–gene interactions in observational population genomics data that are both directed (using local genetic instruments as causal an...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079029/ https://www.ncbi.nlm.nih.gov/pubmed/30082726 http://dx.doi.org/10.1038/s41467-018-05452-6 |
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author | Luijk, René Dekkers, Koen F. van Iterson, Maarten Arindrarto, Wibowo Claringbould, Annique Hop, Paul Boomsma, Dorret I. van Duijn, Cornelia M. van Greevenbroek, Marleen M. J. Veldink, Jan H. Wijmenga, Cisca Franke, Lude ’t Hoen, Peter A. C. Jansen, Rick van Meurs, Joyce Mei, Hailiang Slagboom, P. Eline Heijmans, Bastiaan T. van Zwet, Erik W. |
author_facet | Luijk, René Dekkers, Koen F. van Iterson, Maarten Arindrarto, Wibowo Claringbould, Annique Hop, Paul Boomsma, Dorret I. van Duijn, Cornelia M. van Greevenbroek, Marleen M. J. Veldink, Jan H. Wijmenga, Cisca Franke, Lude ’t Hoen, Peter A. C. Jansen, Rick van Meurs, Joyce Mei, Hailiang Slagboom, P. Eline Heijmans, Bastiaan T. van Zwet, Erik W. |
author_sort | Luijk, René |
collection | PubMed |
description | Identification of causal drivers behind regulatory gene networks is crucial in understanding gene function. Here, we develop a method for the large-scale inference of gene–gene interactions in observational population genomics data that are both directed (using local genetic instruments as causal anchors, akin to Mendelian Randomization) and specific (by controlling for linkage disequilibrium and pleiotropy). Analysis of genotype and whole-blood RNA-sequencing data from 3072 individuals identified 49 genes as drivers of downstream transcriptional changes (Wald P < 7 × 10(−10)), among which transcription factors were overrepresented (Fisher’s P = 3.3 × 10(−7)). Our analysis suggests new gene functions and targets, including for SENP7 (zinc-finger genes involved in retroviral repression) and BCL2A1 (target genes possibly involved in auditory dysfunction). Our work highlights the utility of population genomics data in deriving directed gene expression networks. A resource of trans-effects for all 6600 genes with a genetic instrument can be explored individually using a web-based browser. |
format | Online Article Text |
id | pubmed-6079029 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60790292018-08-08 Genome-wide identification of directed gene networks using large-scale population genomics data Luijk, René Dekkers, Koen F. van Iterson, Maarten Arindrarto, Wibowo Claringbould, Annique Hop, Paul Boomsma, Dorret I. van Duijn, Cornelia M. van Greevenbroek, Marleen M. J. Veldink, Jan H. Wijmenga, Cisca Franke, Lude ’t Hoen, Peter A. C. Jansen, Rick van Meurs, Joyce Mei, Hailiang Slagboom, P. Eline Heijmans, Bastiaan T. van Zwet, Erik W. Nat Commun Article Identification of causal drivers behind regulatory gene networks is crucial in understanding gene function. Here, we develop a method for the large-scale inference of gene–gene interactions in observational population genomics data that are both directed (using local genetic instruments as causal anchors, akin to Mendelian Randomization) and specific (by controlling for linkage disequilibrium and pleiotropy). Analysis of genotype and whole-blood RNA-sequencing data from 3072 individuals identified 49 genes as drivers of downstream transcriptional changes (Wald P < 7 × 10(−10)), among which transcription factors were overrepresented (Fisher’s P = 3.3 × 10(−7)). Our analysis suggests new gene functions and targets, including for SENP7 (zinc-finger genes involved in retroviral repression) and BCL2A1 (target genes possibly involved in auditory dysfunction). Our work highlights the utility of population genomics data in deriving directed gene expression networks. A resource of trans-effects for all 6600 genes with a genetic instrument can be explored individually using a web-based browser. Nature Publishing Group UK 2018-08-06 /pmc/articles/PMC6079029/ /pubmed/30082726 http://dx.doi.org/10.1038/s41467-018-05452-6 Text en © The Author(s) 2018 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 Luijk, René Dekkers, Koen F. van Iterson, Maarten Arindrarto, Wibowo Claringbould, Annique Hop, Paul Boomsma, Dorret I. van Duijn, Cornelia M. van Greevenbroek, Marleen M. J. Veldink, Jan H. Wijmenga, Cisca Franke, Lude ’t Hoen, Peter A. C. Jansen, Rick van Meurs, Joyce Mei, Hailiang Slagboom, P. Eline Heijmans, Bastiaan T. van Zwet, Erik W. Genome-wide identification of directed gene networks using large-scale population genomics data |
title | Genome-wide identification of directed gene networks using large-scale population genomics data |
title_full | Genome-wide identification of directed gene networks using large-scale population genomics data |
title_fullStr | Genome-wide identification of directed gene networks using large-scale population genomics data |
title_full_unstemmed | Genome-wide identification of directed gene networks using large-scale population genomics data |
title_short | Genome-wide identification of directed gene networks using large-scale population genomics data |
title_sort | genome-wide identification of directed gene networks using large-scale population genomics data |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079029/ https://www.ncbi.nlm.nih.gov/pubmed/30082726 http://dx.doi.org/10.1038/s41467-018-05452-6 |
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