Penetrance estimation of Alzheimer disease in SORL1 loss-of-function variant carriers using a family-based strategy and stratification by APOE genotypes.

ABSTRACT:

Background

Alzheimer disease (AD) is a common complex disorder with a high genetic component. Loss-of-function (LoF) SORL1 variants are one of the strongest AD genetic risk factors. Estimating their age-related penetrance is essential before putative use for genetic counseling or preventive trials. However, relative rarity and co-occurrence with the main AD risk factor, APOE-ε4, make such estimations difficult.

Methods

We proposed to estimate the age-related penetrance of SORL1-LoF variants through a survival framework by estimating the conditional instantaneous risk combining (i) a baseline for non-carriers of SORL1-LoF variants, stratified by APOE-ε4, derived from the Rotterdam study (N = 12,255), and (ii) an age-dependent proportional hazard effect for SORL1-LoF variants

SUBMITTER: Schramm C 

PROVIDER: S-EPMC9238165 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature