Dissecting Complex Traits Using Omics Data: A Review on the Linear Mixed Models and Their Application in GWAS

Genome-wide association study (GWAS) is the most popular approach to dissecting complex traits in plants, humans, and animals. Numerous methods and tools have been proposed to discover the causal variants for GWAS data analysis. Among them, linear mixed models (LMMs) are widely used statistical methods for regulating confounding factors, including population structure, resulting in increased computational proficiency and statistical power in GWAS studies. Recently more attention has been paid to pleiotropy, multi-trait, gene-gene interaction, gene-environment interaction, and multi-locus methods with the growing availability of large-scale GWAS data and relevant phenotype samples. In this review, we have demonstrated all possible LMMs-based methods available in the literature for GWAS. We briefly discuss the different LMM methods, software packages, and available open-source applications in GWAS. Then, we include the advantages and weaknesses of the LMMs in GWAS. Finally, we discuss the future perspective and conclusion. The present review paper would be helpful to the researchers for selecting appropriate LMM models and methods quickly for GWAS data analysis and would benefit the scientific society.