Determining the risk of a phenotypic outcome is a complex balance of variants "for" or "against" the phenotype, which in the context of human genetic diseases have been summarized using polygenic risk scores. In a previously published article (K. T. Hellmann, L. Challagundla, B. M. Gray, D. A. Robinson, J Clin Microbiol 61:e01412-22, 2023, https://doi.org/10.1128/jcm.01412-22), Hellmann and colleagues demonstrate how the use of a bacterial polygenic risk score to predict S. epidermidis infection versus colonization in neonates led to both increases in predictive accuracy and improved generalizability to external data.