Fig. 1
Overview of the method for estimating the piecewise constant hazard model. λ(t | a, s) refers to the instantaneous risk to develop the disease depending on age t and genotype (a,s) ∊ APOE × SORL1. λnc(t | a) refers to the specific instantaneous risk associated with non-carriers of the SORL1 variant of interest stratified on APOE genotype and derived from the Rotterdam Study [25]. β(t) refers to the additional effect of the SORL1 variant. λnc(t | a) and β(t) are both piecewise constant over time. E/M-steps refer to expectation/maximization steps. wi(a, s), individual weight updating at each E-step iteration referring to the posterior probability distribution of individual i for combined genotype (a,s); y, years; SORL1+, carrier of the variant of interest in SORL1 gene; SORL1 WT, wild type for SORL1 (non-carriers of the variant of interest); ?, unknown genotype. The red arrow indicates the proband