Polygenic score integrating neurodegenerative and vascular risk informs dementia risk stratification.

ABSTRACT:

Introduction

An integrative polygenic risk score (iPRS) capturing the neurodegenerative and vascular contribution to dementia could identify high-risk individuals and improve risk prediction.

Methods

We developed an iPRS for dementia (iPRS-DEM) in Europeans (aged 65+), comprising genetic risk for Alzheimer's disease (AD) and 23 vascular or neurodegenerative traits (excluding apolipoprotein E [APOE]). iPRS-DEM was evaluated across cohorts comprising older community-dwelling people (N = 3702), a multi-ancestry biobank (N = 130,797 Europeans; 105,404 non-Europeans), and dementia-free memory clinic participants (N = 2032).

Results

iPRS-DEM was associated with dementia risk independently of APOE in the elderly (subdistribution hazard ratio [sHR]_per1SD = 1.15, 95

SUBMITTER: D'Aoust T 

PROVIDER: S-EPMC11881617 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature