Cargando…

Discovering genetic interactions bridging pathways in genome-wide association studies

Genetic interactions have been reported to underlie phenotypes in a variety of systems, but the extent to which they contribute to complex disease in humans remains unclear. In principle, genome-wide association studies (GWAS) provide a platform for detecting genetic interactions, but existing metho...

Descripción completa

Detalles Bibliográficos
Autores principales: Fang, Gang, Wang, Wen, Paunic, Vanja, Heydari, Hamed, Costanzo, Michael, Liu, Xiaoye, Liu, Xiaotong, VanderSluis, Benjamin, Oately, Benjamin, Steinbach, Michael, Van Ness, Brian, Schadt, Eric E., Pankratz, Nathan D., Boone, Charles, Kumar, Vipin, Myers, Chad L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753138/
https://www.ncbi.nlm.nih.gov/pubmed/31537791
http://dx.doi.org/10.1038/s41467-019-12131-7
_version_ 1783452835985227776
author Fang, Gang
Wang, Wen
Paunic, Vanja
Heydari, Hamed
Costanzo, Michael
Liu, Xiaoye
Liu, Xiaotong
VanderSluis, Benjamin
Oately, Benjamin
Steinbach, Michael
Van Ness, Brian
Schadt, Eric E.
Pankratz, Nathan D.
Boone, Charles
Kumar, Vipin
Myers, Chad L.
author_facet Fang, Gang
Wang, Wen
Paunic, Vanja
Heydari, Hamed
Costanzo, Michael
Liu, Xiaoye
Liu, Xiaotong
VanderSluis, Benjamin
Oately, Benjamin
Steinbach, Michael
Van Ness, Brian
Schadt, Eric E.
Pankratz, Nathan D.
Boone, Charles
Kumar, Vipin
Myers, Chad L.
author_sort Fang, Gang
collection PubMed
description Genetic interactions have been reported to underlie phenotypes in a variety of systems, but the extent to which they contribute to complex disease in humans remains unclear. In principle, genome-wide association studies (GWAS) provide a platform for detecting genetic interactions, but existing methods for identifying them from GWAS data tend to focus on testing individual locus pairs, which undermines statistical power. Importantly, a global genetic network mapped for a model eukaryotic organism revealed that genetic interactions often connect genes between compensatory functional modules in a highly coherent manner. Taking advantage of this expected structure, we developed a computational approach called BridGE that identifies pathways connected by genetic interactions from GWAS data. Applying BridGE broadly, we discover significant interactions in Parkinson’s disease, schizophrenia, hypertension, prostate cancer, breast cancer, and type 2 diabetes. Our novel approach provides a general framework for mapping complex genetic networks underlying human disease from genome-wide genotype data.
format Online
Article
Text
id pubmed-6753138
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-67531382019-09-23 Discovering genetic interactions bridging pathways in genome-wide association studies Fang, Gang Wang, Wen Paunic, Vanja Heydari, Hamed Costanzo, Michael Liu, Xiaoye Liu, Xiaotong VanderSluis, Benjamin Oately, Benjamin Steinbach, Michael Van Ness, Brian Schadt, Eric E. Pankratz, Nathan D. Boone, Charles Kumar, Vipin Myers, Chad L. Nat Commun Article Genetic interactions have been reported to underlie phenotypes in a variety of systems, but the extent to which they contribute to complex disease in humans remains unclear. In principle, genome-wide association studies (GWAS) provide a platform for detecting genetic interactions, but existing methods for identifying them from GWAS data tend to focus on testing individual locus pairs, which undermines statistical power. Importantly, a global genetic network mapped for a model eukaryotic organism revealed that genetic interactions often connect genes between compensatory functional modules in a highly coherent manner. Taking advantage of this expected structure, we developed a computational approach called BridGE that identifies pathways connected by genetic interactions from GWAS data. Applying BridGE broadly, we discover significant interactions in Parkinson’s disease, schizophrenia, hypertension, prostate cancer, breast cancer, and type 2 diabetes. Our novel approach provides a general framework for mapping complex genetic networks underlying human disease from genome-wide genotype data. Nature Publishing Group UK 2019-09-19 /pmc/articles/PMC6753138/ /pubmed/31537791 http://dx.doi.org/10.1038/s41467-019-12131-7 Text en © The Author(s) 2019 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
Fang, Gang
Wang, Wen
Paunic, Vanja
Heydari, Hamed
Costanzo, Michael
Liu, Xiaoye
Liu, Xiaotong
VanderSluis, Benjamin
Oately, Benjamin
Steinbach, Michael
Van Ness, Brian
Schadt, Eric E.
Pankratz, Nathan D.
Boone, Charles
Kumar, Vipin
Myers, Chad L.
Discovering genetic interactions bridging pathways in genome-wide association studies
title Discovering genetic interactions bridging pathways in genome-wide association studies
title_full Discovering genetic interactions bridging pathways in genome-wide association studies
title_fullStr Discovering genetic interactions bridging pathways in genome-wide association studies
title_full_unstemmed Discovering genetic interactions bridging pathways in genome-wide association studies
title_short Discovering genetic interactions bridging pathways in genome-wide association studies
title_sort discovering genetic interactions bridging pathways in genome-wide association studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6753138/
https://www.ncbi.nlm.nih.gov/pubmed/31537791
http://dx.doi.org/10.1038/s41467-019-12131-7
work_keys_str_mv AT fanggang discoveringgeneticinteractionsbridgingpathwaysingenomewideassociationstudies
AT wangwen discoveringgeneticinteractionsbridgingpathwaysingenomewideassociationstudies
AT paunicvanja discoveringgeneticinteractionsbridgingpathwaysingenomewideassociationstudies
AT heydarihamed discoveringgeneticinteractionsbridgingpathwaysingenomewideassociationstudies
AT costanzomichael discoveringgeneticinteractionsbridgingpathwaysingenomewideassociationstudies
AT liuxiaoye discoveringgeneticinteractionsbridgingpathwaysingenomewideassociationstudies
AT liuxiaotong discoveringgeneticinteractionsbridgingpathwaysingenomewideassociationstudies
AT vandersluisbenjamin discoveringgeneticinteractionsbridgingpathwaysingenomewideassociationstudies
AT oatelybenjamin discoveringgeneticinteractionsbridgingpathwaysingenomewideassociationstudies
AT steinbachmichael discoveringgeneticinteractionsbridgingpathwaysingenomewideassociationstudies
AT vannessbrian discoveringgeneticinteractionsbridgingpathwaysingenomewideassociationstudies
AT schadterice discoveringgeneticinteractionsbridgingpathwaysingenomewideassociationstudies
AT pankratznathand discoveringgeneticinteractionsbridgingpathwaysingenomewideassociationstudies
AT boonecharles discoveringgeneticinteractionsbridgingpathwaysingenomewideassociationstudies
AT kumarvipin discoveringgeneticinteractionsbridgingpathwaysingenomewideassociationstudies
AT myerschadl discoveringgeneticinteractionsbridgingpathwaysingenomewideassociationstudies