One of the most challenging aspects of moving PRS to the clinical arena is ensuring that they are equally applicable to all health care users across ethnic groups to limit exacerbating health disparities [21]. This is an important issue both for minority ethnic groups within high-income countries, who may be under-represented in research studies, and for low- and middle-income countries, where genetic studies of the relevant ancestry may not exist because of limited research infrastructure. Current PRS methods rely on an individual’s genetic ancestry being similar to the large GWAS study from which reference effect sizes are taken for PRS calculation and may require access to an ancestry-matched genotype-level reference panel. Such studies are currently only widely available in European ancestries [22, 23], so polygenic risk scores are applicable to only a small proportion of the world’s population; in this paper, unless otherwise stated, study participants are of European ancestries. Transferability of PRS across populations is limited, with PRS generated from GWAS in one population usually providing attenuated predictive accuracy in other populations [21, 24]. Reasons for this include the
