Journal
BRIEFINGS IN BIOINFORMATICS
Volume 10, Issue 6, Pages 664-675Publisher
OXFORD UNIV PRESS
DOI: 10.1093/bib/bbp050
Keywords
mixed model; association study; quantitative trait loci; genome-wide; kinship; population structure
Funding
- NSF-Plant Genome Program [DBI-0321467, 0703908, 0820619]
- NSF-Plant Genome Comparative Sequencing Program [DBI-06638566]
- USDA-ARS
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Mixed models improve the ability to detect phenotype-genotype associations in the presence of population stratification and multiple levels of relatedness in genome-wide association studies (GWAS), but for large data sets the resource consumption becomes impractical. At the same time, the sample size and number of markers used for GWAS is increasing dramatically, resulting in greater statistical power to detect those associations. The use of mixed models with increasingly large data sets depends on the availability of software for analyzing those models. While multiple software packages implement the mixed model method, no single package provides the best combination of fast computation, ability to handle large samples, flexible modeling and ease of use. Key elements of association analysis with mixed models are reviewed, including modeling phenotype-genotype associations using mixed models, population stratification, kinship and its estimation, variance component estimation, use of best linear unbiased predictors or residuals in place of raw phenotype, improving efficiency and software-user interaction. The available software packages are evaluated, and suggestions made for future software development.
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