Beyond the standard GWAS - a guide for plant biologists.

ABSTRACT

Classic genome-wide association studies (GWAS) look for associations between individual SNPs and phenotypes of interest. With the rapid progress of high-throughput genotyping and phenotyping technologies, GWAS have become increasingly powerful for detecting genetic determinants and their molecular mechanisms underpinning natural phenotypic variation. However, GWAS frequently yield results with neither expected nor promising loci, nor any significant associations. This is often because associations between SNPs and a single phenotype are confounded, for example with the environment, other traits, or complex genetic structures. Such confounding can mask true genotype-phenotype associations, or inflate spurious associations. To address these problems, numerous methods have been developed that go beyond the standard model. Such advanced GWAS models are flexible and can offer improved statistical power for understanding the genetics underlying complex traits. Despite this advantage, these models have not been widely adopted and implemented compared to the standard GWAS approach, partly because this literature is diverse and often technical. In this review, our aim is to provide an overview of the application and the benefits of various advanced GWAS models for handling complex traits and genetic structures, targeting plant biologists who wish to carry out GWAS more effectively.