In order to effectively use PRS in the practice of psychiatry, it is critically important to understand the limitations of this measure and considerations for interpretation of PRS which we aim to highlight here. First, PRS are highly sensitive to ethnic background—meaning that variability in a PRS can be heavily influenced by allele frequency differences, differences in estimated effect sizes, and differences in population structure across different ethnic groups 16, 17. For instance, if a disease-associated risk variant is common in one population but a low frequency in another population (for example, the “A” allele frequency is 20% in the general population of ethnic group X versus 5% in ethnic group Y), then the likelihood of an individual from ethnic group X carrying one or more risk alleles by chance is much higher than for an individual from ethnic group Y (that is, 36% versus 10%, based on the principles of Hardy–Weinberg equilibrium where f(AA+Aa) = p 2+2pq). Furthermore, owing to differences in population history (including effective population size and distinctive rates of immigration and inbreeding), inheritance patterns of genomic
