Patient stratification by genetic risk in Alzheimer's disease is only effective in the presence of phenotypic heterogeneity.

ABSTRACT: Case-only designs in longitudinal cohorts are a valuable resource for identifying disease-relevant genes, pathways, and novel targets influencing disease progression. This is particularly relevant in Alzheimer's disease (AD), where longitudinal cohorts measure disease "progression," defined by rate of cognitive decline. Few of the identified drug targets for AD have been clinically tractable, and phenotypic heterogeneity is an obstacle to both clinical research and basic science. In four cohorts (n = 7241), we performed genome-wide association studies (GWAS) and Mendelian randomization (MR) to discover novel targets associated with progression and assess causal relationships. We tested opportunities for patient stratification by deriving polygenic risk scores (PRS) for AD risk and severity

SUBMITTER: Euesden J 

PROVIDER: S-EPMC11717250 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature