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A gene based approach to test genetic association based on an optimally weighted combination of multiple traits

There is increasing evidence showing that pleiotropy is a widespread phenomenon in complex diseases for which multiple correlated traits are often measured. Joint analysis of multiple traits could increase statistical power by aggregating multiple weak effects. Existing methods for multiple trait as...

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Detalles Bibliográficos
Autores principales: Zhang, Jianjun, Sha, Qiuying, Liu, Guanfu, Wang, Xuexia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688794/
https://www.ncbi.nlm.nih.gov/pubmed/31398229
http://dx.doi.org/10.1371/journal.pone.0220914
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author Zhang, Jianjun
Sha, Qiuying
Liu, Guanfu
Wang, Xuexia
author_facet Zhang, Jianjun
Sha, Qiuying
Liu, Guanfu
Wang, Xuexia
author_sort Zhang, Jianjun
collection PubMed
description There is increasing evidence showing that pleiotropy is a widespread phenomenon in complex diseases for which multiple correlated traits are often measured. Joint analysis of multiple traits could increase statistical power by aggregating multiple weak effects. Existing methods for multiple trait association tests usually study each of the multiple traits separately and then combine the univariate test statistics or combine p-values of the univariate tests for identifying disease associated genetic variants. However, ignoring correlation between phenotypes may cause power loss. Additionally, the genetic variants in one gene (including common and rare variants) are often viewed as a whole that affects the underlying disease since the basic functional unit of inheritance is a gene rather than a genetic variant. Thus, results from gene level association tests can be more readily integrated with downstream functional and pathogenic investigation, whereas many existing methods for multiple trait association tests only focus on testing a single common variant rather than a gene. In this article, we propose a statistical method by Testing an Optimally Weighted Combination of Multiple traits (TOW-CM) to test the association between multiple traits and multiple variants in a genomic region (a gene or pathway). We investigate the performance of the proposed method through extensive simulation studies. Our simulation studies show that the proposed method has correct type I error rates and is either the most powerful test or comparable with the most powerful tests. Additionally, we illustrate the usefulness of TOW-CM based on a COPDGene study.
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spelling pubmed-66887942019-08-15 A gene based approach to test genetic association based on an optimally weighted combination of multiple traits Zhang, Jianjun Sha, Qiuying Liu, Guanfu Wang, Xuexia PLoS One Research Article There is increasing evidence showing that pleiotropy is a widespread phenomenon in complex diseases for which multiple correlated traits are often measured. Joint analysis of multiple traits could increase statistical power by aggregating multiple weak effects. Existing methods for multiple trait association tests usually study each of the multiple traits separately and then combine the univariate test statistics or combine p-values of the univariate tests for identifying disease associated genetic variants. However, ignoring correlation between phenotypes may cause power loss. Additionally, the genetic variants in one gene (including common and rare variants) are often viewed as a whole that affects the underlying disease since the basic functional unit of inheritance is a gene rather than a genetic variant. Thus, results from gene level association tests can be more readily integrated with downstream functional and pathogenic investigation, whereas many existing methods for multiple trait association tests only focus on testing a single common variant rather than a gene. In this article, we propose a statistical method by Testing an Optimally Weighted Combination of Multiple traits (TOW-CM) to test the association between multiple traits and multiple variants in a genomic region (a gene or pathway). We investigate the performance of the proposed method through extensive simulation studies. Our simulation studies show that the proposed method has correct type I error rates and is either the most powerful test or comparable with the most powerful tests. Additionally, we illustrate the usefulness of TOW-CM based on a COPDGene study. Public Library of Science 2019-08-09 /pmc/articles/PMC6688794/ /pubmed/31398229 http://dx.doi.org/10.1371/journal.pone.0220914 Text en © 2019 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhang, Jianjun
Sha, Qiuying
Liu, Guanfu
Wang, Xuexia
A gene based approach to test genetic association based on an optimally weighted combination of multiple traits
title A gene based approach to test genetic association based on an optimally weighted combination of multiple traits
title_full A gene based approach to test genetic association based on an optimally weighted combination of multiple traits
title_fullStr A gene based approach to test genetic association based on an optimally weighted combination of multiple traits
title_full_unstemmed A gene based approach to test genetic association based on an optimally weighted combination of multiple traits
title_short A gene based approach to test genetic association based on an optimally weighted combination of multiple traits
title_sort gene based approach to test genetic association based on an optimally weighted combination of multiple traits
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6688794/
https://www.ncbi.nlm.nih.gov/pubmed/31398229
http://dx.doi.org/10.1371/journal.pone.0220914
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