Prioritizing the detection of rare pathogenic variants in population screening

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.

Automated summary

Population genomic screening for detecting carriers of rare monogenic variants with medically actionable conditions is well-supported by evidence of clinical utility and cost effectiveness. However, less evidence supports the use of polygenic risk scores in screening, as they do not detect rare variants. Relying solely on polygenic scores for population screening without considering the detection of high-risk rare monogenic variants is not recommended, as cautioned by Lacaze et al.