Escott-Price V, Schmidt KM, et al. - This study’s findings demonstrate that this method accounts for the varying disease prevalence in different genotypes and age groups when modelling the APOE and rare genetic variants risk in addition to polygenic risk score (PRS). The results indicate that this approach is very effective for use in a clinical setting and can easily be updated for novel rare variants and for other populations or confounding factors when appropriate genome-wide association data become available.

• It has been reported that Alzheimer disease (AD) probability varies with respect to age, APOE status, and the presence of rare variants.

• Results showed that the probability of AD grows from 0.03 to 0.18 (without APOE) and 0.07 to 0.7 (APOE e4e4 carriers) as PRS increases in the age group 65+.

• These values are 0.08–0.6 and 0.3–0.85 in 85+.

• In the age group 65+, the probability may be increased by the presence of rare mutations, e.g. in TREM2 from 0.02 at the negative tail of the PRS to 0.3.