The GWAS association of genotypes with healthcare costs is of great interest. However, it is unclear that “quantifying expenditure associated with pathogenic variants or elevated polygenic risk can inform the cost-effectiveness of screening and other interventions.” Observational cost estimates reported in the paper reflect average healthcare use for individuals with and without clinical diagnoses and with or without the adoption of prevention strategies. The paper states, “we estimate that BRCA2 loss-of-function carriers alone account for an additional €17.4 million (£15.1 million) in annual inpatient costs. Importantly, these estimates capture cumulative healthcare expenditures incurred across conditions and over time, rather than costs attributable to a single cancer diagnosis. As such, they provide empirically grounded inputs for decision-analytic models, including those evaluating screening and preventive interventions, which often rely on simplified assumptions about disease incidence or treatment costs.”

However, a cost-effectiveness model of screening needs to model expected costs with and without diagnoses established through screening. Average costs for individuals with BRCA1/2 variants relative to individuals with other genotypes does not indicate how costs change with earlier diagnosis and management.