This effect is long established for highly detrimental variants such as the BRCA1/2 gene mutations in the case of breast cancer (Kuchenbaecker et al., 2017) and the APOE e4 allele in the case of AD (Farrer et al., 1997), where these gene variant carriers are known to be present in lower numbers among older undiagnosed individuals. This evidence concerns the gene APOE and Alzheimer disease.