title: The Use of Targeted Marker Subsets to Account for Population Structure and Relatedness in Genome-Wide Association Studies of Maize (Zea mays L.).
abstract: A typical plant genome-wide association study (GWAS) uses a mixed linear model (MLM) that includes a trait as the response variable, a marker as an explanatory variable, and fixed and random effect covariates accounting for population structure and relatedness. Although effective in controlling for false positive signals, this model typically fails to detect signals that are correlated with population structure or are located in high linkage disequilibrium (LD) genomic regions. This result likely arises from each tested marker being used to estimate population structure and relatedness. Previous work has demonstrated that it is possible to increase the power of the MLM by estimating relatedness (i.e., kinship) with markers that are not located on the chromosome where the tested marker resides. To quantify the amount of additional significant signals one can expect using this so-called K_chr model, we reanalyzed Mendelian, polygenic, and complex traits in two maize (Zea mays L.) diversity panels that have been previously assessed using the traditional MLM. We demonstrated that the K_chr model could find more significant associations, especially in high LD regions. This finding is underscored by our identification of novel genomic signals proximal to the tocochromanol biosynthetic pathway gene ZmVTE1 that are associated with a ratio of tocotrienols. We conclude that the K_chr model can detect more intricate sources of allelic variation underlying agronomically important traits, and should therefore become more widely used for GWAS. To facilitate the implementation of the K_chr model, we provide code written in the R programming language.
authors.affiliation: Department of Statistics, University of Illinois at Urbana-Champaign, Illinois 61801.
authors.forename: Angela H
authors.initials: AH
authors.lastname: Chen
authors.affiliation: Department of Crop Sciences, University of Illinois at Urbana-Champaign, Illinois 61801 alipka@illinois.edu.
authors.forename: Alexander E
authors.identifier: 0000-0003-1571-8528
authors.initials: AE
authors.lastname: Lipka
mesh_terms: D000483:Alleles; D002874:Chromosome Mapping; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D023281:Genomics; D015810:Linkage Disequilibrium; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*; D003313:Zea mays / Q000235:genetics*
keywords: GWAS; linkage disequilibrium; maize; marker subsets; mixed model