Whole genome sequencing is increasingly used to study phenotypic variation among infectious pathogens and to
evaluate their relative transmissibility, virulence, and immunogenicity. To date, relatively little has been published on
how and how many pathogen strains should be selected for studies associating phenotype and genotype. There
are specific challenges when identifying genetic associations in bacteria which often comprise highly structured
populations. Here we consider general methodological questions related to sampling and analysis focusing on
clonal to moderately recombining pathogens. We propose that a matched sampling scheme constitutes an
efficient study design, and provide a power calculator based on phylogenetic convergence. We demonstrate this
approach by applying it to genomic datasets for two microbial pathogens: Mycobacterium tuberculosis and
Campylobacter species.