Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1782341396627193856 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4210555 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT limeng enrichmentofstatisticalpowerforgenomewideassociationstudies AT liuxiaolei enrichmentofstatisticalpowerforgenomewideassociationstudies AT bradburypeter enrichmentofstatisticalpowerforgenomewideassociationstudies AT yujianming enrichmentofstatisticalpowerforgenomewideassociationstudies AT zhangyuanming enrichmentofstatisticalpowerforgenomewideassociationstudies AT todhunterroryj enrichmentofstatisticalpowerforgenomewideassociationstudies AT buckleredwards enrichmentofstatisticalpowerforgenomewideassociationstudies AT zhangzhiwu enrichmentofstatisticalpowerforgenomewideassociationstudies |