Integrating rare pathogenic variant prioritization with gene-based association analysis to identify novel genes and relevant multimodal traits for Alzheimer's disease.

ABSTRACT:

Introduction

Increasing evidence has highlighted rare variants in Alzheimer's disease (AD). However, insufficient sample sizes, especially in underrepresented ethnic groups, hinder their investigation. Additionally, their impact on endophenotypes remains largely unexplored.

Methods

We prioritized rare likely-deleterious variants based on whole-genome sequencing data from a Chinese AD cohort (n = 988). Gene-based optimal sequence kernel association tests were conducted between AD cases and normal controls to identify AD-related genes. Network clustering, endophenotype association, and cellular experiments were conducted to evaluate their functional consequences.

Results

We identified 11 novel AD candidate genes, which captured AD-related pathways and enhanced AD risk p

SUBMITTER: Cao J 

PROVIDER: S-EPMC11851317 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature