The potential value of polygenic scores is supported by the increasing number of research studies that show a highly significant association between PRS and disease status, but their clinical utility has yet to be established. Can PRS be used by clinicians for disease prediction or stratification, either now or in the future? For this to be achieved, the focus must shift from association with case-control status to the information in the PRS for a single individual. Furthermore, to translate PRS to clinical tools, relative risks that compare individuals across the PRS continuum with a baseline group will eventually need to be transformed to absolute risks for the disease [34, 35]. Unlike monogenic disorders caused by high-penetrance mutations, in complex disorders, the discriminative ability of PRS is compromised by the multifactorial contributors to the disease, the imperfect measurement of the full genetic signal, and the potentially incorrect measurement.
