While PRSs on most complex traits presently have limited power to accurately predict risk at the individual level, which will remain the case for low-to-moderate–heritability traits irrespective of GWAS sample sizes, recent studies have demonstrated that individuals at the tails of PRS distribution can have substantially higher disease risk than those of the general population. Thus, these individuals may provide useful subjects for experimental follow-up, while in clinical settings it could be more efficacious to use different risk management strategies, in terms of screening or interventions, for example, for individuals with extreme PRS [1–3].
