Causal association of cognitive reserve on Alzheimer's disease with putative sex difference.

ABSTRACT:

Introduction

Sex-dependent risk factors may underlie sex differences in Alzheimer's disease (AD).

Methods

Using sex-stratified genome-wide association studies (GWAS) of AD, we evaluated associations of 12 traits with AD through polygenic risk scores (PRS) and Mendelian randomization (MR), and explored joint genetic architecture among significant traits by genomic structural equation modeling and network analysis.

Results

AD was associated with lower PRS for premorbid cognitive performance, intelligence, and educational attainment. MR showed a causal role for the cognition-related traits in AD, particularly among females. Their joint genetic components encompassed RNA processing, neuron projection development, and cell cycle pathways that overlap with cellular senescen

SUBMITTER: Wang H 

PROVIDER: S-EPMC8719428 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature