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GWAB: a web server for the network-based boosting of human genome-wide association data

During the last decade, genome-wide association studies (GWAS) have represented a major approach to dissect complex human genetic diseases. Due in part to limited statistical power, most studies identify only small numbers of candidate genes that pass the conventional significance thresholds (e.g. P...

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Autores principales: Shim, Jung Eun, Bang, Changbae, Yang, Sunmo, Lee, Tak, Hwang, Sohyun, Kim, Chan Yeong, Singh-Blom, U. Martin, Marcotte, Edward M., Lee, Insuk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793838/
https://www.ncbi.nlm.nih.gov/pubmed/28449091
http://dx.doi.org/10.1093/nar/gkx284
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author Shim, Jung Eun
Bang, Changbae
Yang, Sunmo
Lee, Tak
Hwang, Sohyun
Kim, Chan Yeong
Singh-Blom, U. Martin
Marcotte, Edward M.
Lee, Insuk
author_facet Shim, Jung Eun
Bang, Changbae
Yang, Sunmo
Lee, Tak
Hwang, Sohyun
Kim, Chan Yeong
Singh-Blom, U. Martin
Marcotte, Edward M.
Lee, Insuk
author_sort Shim, Jung Eun
collection PubMed
description During the last decade, genome-wide association studies (GWAS) have represented a major approach to dissect complex human genetic diseases. Due in part to limited statistical power, most studies identify only small numbers of candidate genes that pass the conventional significance thresholds (e.g. P ≤ 5 × 10(−8)). This limitation can be partly overcome by increasing the sample size, but this comes at a higher cost. Alternatively, weak association signals can be boosted by incorporating independent data. Previously, we demonstrated the feasibility of boosting GWAS disease associations using gene networks. Here, we present a web server, GWAB (www.inetbio.org/gwab), for the network-based boosting of human GWAS data. Using GWAS summary statistics (P-values) for SNPs along with reference genes for a disease of interest, GWAB reprioritizes candidate disease genes by integrating the GWAS and network data. We found that GWAB could more effectively retrieve disease-associated reference genes than GWAS could alone. As an example, we describe GWAB-boosted candidate genes for coronary artery disease and supporting data in the literature. These results highlight the inherent value in sub-threshold GWAS associations, which are often not publicly released. GWAB offers a feasible general approach to boost such associations for human disease genetics.
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spelling pubmed-57938382018-02-06 GWAB: a web server for the network-based boosting of human genome-wide association data Shim, Jung Eun Bang, Changbae Yang, Sunmo Lee, Tak Hwang, Sohyun Kim, Chan Yeong Singh-Blom, U. Martin Marcotte, Edward M. Lee, Insuk Nucleic Acids Res Web Server Issue During the last decade, genome-wide association studies (GWAS) have represented a major approach to dissect complex human genetic diseases. Due in part to limited statistical power, most studies identify only small numbers of candidate genes that pass the conventional significance thresholds (e.g. P ≤ 5 × 10(−8)). This limitation can be partly overcome by increasing the sample size, but this comes at a higher cost. Alternatively, weak association signals can be boosted by incorporating independent data. Previously, we demonstrated the feasibility of boosting GWAS disease associations using gene networks. Here, we present a web server, GWAB (www.inetbio.org/gwab), for the network-based boosting of human GWAS data. Using GWAS summary statistics (P-values) for SNPs along with reference genes for a disease of interest, GWAB reprioritizes candidate disease genes by integrating the GWAS and network data. We found that GWAB could more effectively retrieve disease-associated reference genes than GWAS could alone. As an example, we describe GWAB-boosted candidate genes for coronary artery disease and supporting data in the literature. These results highlight the inherent value in sub-threshold GWAS associations, which are often not publicly released. GWAB offers a feasible general approach to boost such associations for human disease genetics. Oxford University Press 2017-07-03 2017-04-26 /pmc/articles/PMC5793838/ /pubmed/28449091 http://dx.doi.org/10.1093/nar/gkx284 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Web Server Issue
Shim, Jung Eun
Bang, Changbae
Yang, Sunmo
Lee, Tak
Hwang, Sohyun
Kim, Chan Yeong
Singh-Blom, U. Martin
Marcotte, Edward M.
Lee, Insuk
GWAB: a web server for the network-based boosting of human genome-wide association data
title GWAB: a web server for the network-based boosting of human genome-wide association data
title_full GWAB: a web server for the network-based boosting of human genome-wide association data
title_fullStr GWAB: a web server for the network-based boosting of human genome-wide association data
title_full_unstemmed GWAB: a web server for the network-based boosting of human genome-wide association data
title_short GWAB: a web server for the network-based boosting of human genome-wide association data
title_sort gwab: a web server for the network-based boosting of human genome-wide association data
topic Web Server Issue
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793838/
https://www.ncbi.nlm.nih.gov/pubmed/28449091
http://dx.doi.org/10.1093/nar/gkx284
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