Prioritizing the detection of rare pathogenic variants in population screening

Abstract

Population genomic screening to detect carriers of rare monogenic variants for medically actionable conditions is supported by substantial evidence of clinical utility and cost effectiveness. Much less evidence supports screening by polygenic risk scores, which do not detect rare variants. Using only polygenic scores in population screening initiatives, while ignoring the detection of higher-risk rare monogenic variants, is ill-advised. Lacaze et al. caution against the use of polygenic scores alone for population screening in the absence of monogenic testing.