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Enrichment of statistical power for genome-wide association studies

BACKGROUND: The inheritance of most human diseases and agriculturally important traits is controlled by many genes with small effects. Identifying these genes, while simultaneously controlling false positives, is challenging. Among available statistical methods, the mixed linear model (MLM) has been...

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Autores principales: Li, Meng, Liu, Xiaolei, Bradbury, Peter, Yu, Jianming, Zhang, Yuan-Ming, Todhunter, Rory J, Buckler, Edward S, Zhang, Zhiwu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210555/
https://www.ncbi.nlm.nih.gov/pubmed/25322753
http://dx.doi.org/10.1186/s12915-014-0073-5
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author Li, Meng
Liu, Xiaolei
Bradbury, Peter
Yu, Jianming
Zhang, Yuan-Ming
Todhunter, Rory J
Buckler, Edward S
Zhang, Zhiwu
author_facet Li, Meng
Liu, Xiaolei
Bradbury, Peter
Yu, Jianming
Zhang, Yuan-Ming
Todhunter, Rory J
Buckler, Edward S
Zhang, Zhiwu
author_sort Li, Meng
collection PubMed
description BACKGROUND: The inheritance of most human diseases and agriculturally important traits is controlled by many genes with small effects. Identifying these genes, while simultaneously controlling false positives, is challenging. Among available statistical methods, the mixed linear model (MLM) has been the most flexible and powerful for controlling population structure and individual unequal relatedness (kinship), the two common causes of spurious associations. The introduction of the compressed MLM (CMLM) method provided additional opportunities for optimization by adding two new model parameters: grouping algorithms and number of groups. RESULTS: This study introduces another model parameter to develop an enriched CMLM (ECMLM). The parameter involves algorithms to define kinship between groups (that is, kinship algorithms). The ECMLM calculates kinship using several different algorithms and then chooses the best combination between kinship algorithms and grouping algorithms. CONCLUSION: Simulations show that the ECMLM increases statistical power. In some cases, the magnitude of power gained by using ECMLM instead of CMLM is larger than the improvement found by using CMLM instead of MLM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12915-014-0073-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-42105552014-11-06 Enrichment of statistical power for genome-wide association studies Li, Meng Liu, Xiaolei Bradbury, Peter Yu, Jianming Zhang, Yuan-Ming Todhunter, Rory J Buckler, Edward S Zhang, Zhiwu BMC Biol Methodology Article BACKGROUND: The inheritance of most human diseases and agriculturally important traits is controlled by many genes with small effects. Identifying these genes, while simultaneously controlling false positives, is challenging. Among available statistical methods, the mixed linear model (MLM) has been the most flexible and powerful for controlling population structure and individual unequal relatedness (kinship), the two common causes of spurious associations. The introduction of the compressed MLM (CMLM) method provided additional opportunities for optimization by adding two new model parameters: grouping algorithms and number of groups. RESULTS: This study introduces another model parameter to develop an enriched CMLM (ECMLM). The parameter involves algorithms to define kinship between groups (that is, kinship algorithms). The ECMLM calculates kinship using several different algorithms and then chooses the best combination between kinship algorithms and grouping algorithms. CONCLUSION: Simulations show that the ECMLM increases statistical power. In some cases, the magnitude of power gained by using ECMLM instead of CMLM is larger than the improvement found by using CMLM instead of MLM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12915-014-0073-5) contains supplementary material, which is available to authorized users. BioMed Central 2014-10-17 /pmc/articles/PMC4210555/ /pubmed/25322753 http://dx.doi.org/10.1186/s12915-014-0073-5 Text en © Li et al.; licensee BioMed Central Ltd. 2014 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 work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Methodology Article
Li, Meng
Liu, Xiaolei
Bradbury, Peter
Yu, Jianming
Zhang, Yuan-Ming
Todhunter, Rory J
Buckler, Edward S
Zhang, Zhiwu
Enrichment of statistical power for genome-wide association studies
title Enrichment of statistical power for genome-wide association studies
title_full Enrichment of statistical power for genome-wide association studies
title_fullStr Enrichment of statistical power for genome-wide association studies
title_full_unstemmed Enrichment of statistical power for genome-wide association studies
title_short Enrichment of statistical power for genome-wide association studies
title_sort enrichment of statistical power for genome-wide association studies
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210555/
https://www.ncbi.nlm.nih.gov/pubmed/25322753
http://dx.doi.org/10.1186/s12915-014-0073-5
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