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Finding associated variants in genome-wide association studies on multiple traits

MOTIVATION: Many variants identified by genome-wide association studies (GWAS) have been found to affect multiple traits, either directly or through shared pathways. There is currently a wealth of GWAS data collected in numerous phenotypes, and analyzing multiple traits at once can increase power to...

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Autores principales: Gai, Lisa, Eskin, Eleazar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022769/
https://www.ncbi.nlm.nih.gov/pubmed/29949991
http://dx.doi.org/10.1093/bioinformatics/bty249
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author Gai, Lisa
Eskin, Eleazar
author_facet Gai, Lisa
Eskin, Eleazar
author_sort Gai, Lisa
collection PubMed
description MOTIVATION: Many variants identified by genome-wide association studies (GWAS) have been found to affect multiple traits, either directly or through shared pathways. There is currently a wealth of GWAS data collected in numerous phenotypes, and analyzing multiple traits at once can increase power to detect shared variant effects. However, traditional meta-analysis methods are not suitable for combining studies on different traits. When applied to dissimilar studies, these meta-analysis methods can be underpowered compared to univariate analysis. The degree to which traits share variant effects is often not known, and the vast majority of GWAS meta-analysis only consider one trait at a time. RESULTS: Here, we present a flexible method for finding associated variants from GWAS summary statistics for multiple traits. Our method estimates the degree of shared effects between traits from the data. Using simulations, we show that our method properly controls the false positive rate and increases power when an effect is present in a subset of traits. We then apply our method to the North Finland Birth Cohort and UK Biobank datasets using a variety of metabolic traits and discover novel loci. AVAILABILITY AND IMPLEMENTATION: Our source code is available at https://github.com/lgai/CONFIT. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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spelling pubmed-60227692018-07-05 Finding associated variants in genome-wide association studies on multiple traits Gai, Lisa Eskin, Eleazar Bioinformatics Ismb 2018–Intelligent Systems for Molecular Biology Proceedings MOTIVATION: Many variants identified by genome-wide association studies (GWAS) have been found to affect multiple traits, either directly or through shared pathways. There is currently a wealth of GWAS data collected in numerous phenotypes, and analyzing multiple traits at once can increase power to detect shared variant effects. However, traditional meta-analysis methods are not suitable for combining studies on different traits. When applied to dissimilar studies, these meta-analysis methods can be underpowered compared to univariate analysis. The degree to which traits share variant effects is often not known, and the vast majority of GWAS meta-analysis only consider one trait at a time. RESULTS: Here, we present a flexible method for finding associated variants from GWAS summary statistics for multiple traits. Our method estimates the degree of shared effects between traits from the data. Using simulations, we show that our method properly controls the false positive rate and increases power when an effect is present in a subset of traits. We then apply our method to the North Finland Birth Cohort and UK Biobank datasets using a variety of metabolic traits and discover novel loci. AVAILABILITY AND IMPLEMENTATION: Our source code is available at https://github.com/lgai/CONFIT. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. Oxford University Press 2018-07-01 2018-06-27 /pmc/articles/PMC6022769/ /pubmed/29949991 http://dx.doi.org/10.1093/bioinformatics/bty249 Text en © The Author(s) 2018. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial 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 Ismb 2018–Intelligent Systems for Molecular Biology Proceedings
Gai, Lisa
Eskin, Eleazar
Finding associated variants in genome-wide association studies on multiple traits
title Finding associated variants in genome-wide association studies on multiple traits
title_full Finding associated variants in genome-wide association studies on multiple traits
title_fullStr Finding associated variants in genome-wide association studies on multiple traits
title_full_unstemmed Finding associated variants in genome-wide association studies on multiple traits
title_short Finding associated variants in genome-wide association studies on multiple traits
title_sort finding associated variants in genome-wide association studies on multiple traits
topic Ismb 2018–Intelligent Systems for Molecular Biology Proceedings
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6022769/
https://www.ncbi.nlm.nih.gov/pubmed/29949991
http://dx.doi.org/10.1093/bioinformatics/bty249
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