Microbial genome-wide association studies: lessons from human GWAS

Key Points Genome-wide association studies (GWAS) have been highly successful in the analyses of human genomic data. The increased availability of microorganism whole genomes provides the opportunity for microbial GWAS. Initial microbial GWAS have had success identifying variants for traits under strong selection, such as drug resistance, in a range of bacteria, viruses and protozoa. Several challenges to microbial GWAS exist that could hinder identifying variants under moderate selection. The primary challenge is the increased population stratification in microorganisms owing to selection and complex recombination patterns. Novel software that is tailored to the needs of microbial GWAS would greatly expedite progress in the field. In particular, the application of polygenic methods has yet to be evaluated in microorganisms. An exciting future area of research is the generation of host and microbial genomics data within the same samples. This will allow for genome-to-genome analyses to test for host–microorganism interactions. With the increasing availability of microbial whole genomes, researchers are beginning to carry out genome-wide association studies (GWAS) in bacteria, viruses and protozoa. In this Review, the authors discuss the specific challenges and considerations associated with the application of GWAS methods to microorganisms and consider the future of microbial GWAS in the light of lessons learned from human studies. The reduced costs of sequencing have led to whole-genome sequences for a large number of microorganisms, enabling the application of microbial genome-wide association studies (GWAS). Given the successes of human GWAS in understanding disease aetiology and identifying potential drug targets, microbial GWAS are likely to further advance our understanding of infectious diseases. These advances include insights into pressing global health problems, such as antibiotic resistance and disease transmission. In this Review, we outline the methodologies of GWAS, the current state of the field of microbial GWAS, and how lessons from human GWAS can direct the future of the field.