Genetic regulation of the metabolome differs by sex, Alzheimer's disease stage, and plasma biomarker status.

ABSTRACT:

Introduction

We investigated genetic regulators of circulating plasma metabolites to identify pathways underlying biochemical changes in clinical and biomarker-supported Alzheimer's disease (AD).

Methods

We computed metabolite quantitative trait loci (QTL) with whole-genome sequencing (WGS) and small molecule plasma metabolites from 229 older adults with clinical AD and 322 age-matched healthy controls. Unbiased associations between 6881 metabolites and 332,772 common genetic variants were tested, adjusted for age, sex, and both metabolomic and genomic principal components.

Results

We identified 72 SNP-metabolite associations spanning 66 genes and 12 metabolite classes, including PYROXD2/N6-methyllysine, FAAH/myristoylglycine, and FADS2/arachidonic acid. Additionally,

SUBMITTER: Eissman JM 

PROVIDER: S-EPMC12617352 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature