Late enrollment can hide early disease

The denominator should include carriers eligible for observation before recruitment, not only those alive and enrolled at the analysis baseline. In the population-carrier study indexed as PMID 41130550, age-specific risk estimates need an explicit entry-time model because enrollment at older ages can exclude carriers who died, developed severe disease, or became unavailable earlier. Reporting delayed-entry assumptions and comparing enrolled carriers with genotype-positive nonparticipants would bound this survivor-selection problem. Otherwise, lower observed penetrance may reflect who reached recruitment rather than who remained disease-free.