ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Genetic regulation of the metabolome differs by sex, Alzheimer's disease stage, and plasma biomarker status.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Seipin modulates Alzheimer's disease pathogenesis by regulating ferroptosis through a glycine-mediated metabolic pathway.Metabolic brain disease · 2026Article
- Shared Risk Genes and Casual Relationships across Sex Hormone Related Traits and Alzheimer's Disease.medRxiv : the preprint server for health sciences · 2026Article
- Genetic regulation of the metabolome differs by sex, Alzheimer's disease stage, and plasma biomarker status.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
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Abstract
introductionWe investigated genetic regulators of circulating plasma metabolites to identify pathways underlying biochemical changes in clinical and biomarker-supported Alzheimer's disease (AD).
methodsWe 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.
resultsWe identified 72 SNP-metabolite associations spanning 66 genes and 12 metabolite classes, including PYROXD2/N6-methyllysine, FAAH/myristoylglycine, and FADS2/arachidonic acid. Additionally, we found differences in genetic regulation of metabolites among individuals with clinically-defined AD compared to biomarker-defined AD based on a published plasma P-tau181 cutoff. We also found more SNP-metabolite associations among males compared to females. DISCUSSION: In summary, we identified sex- and disease-specific genetic regulators of plasma metabolites, revealing unique biological mechanisms of genetic perturbations in AD. HIGHLIGHTS: Genetic regulators of the metabolome spanned 66 genes and 12 metabolite classes. Clinically versus biomarker-defined Alzheimer's disease (AD) affects genetic regulators of the metabolome. Most metabolite quantitative trait loci (QTLs) are not shared between males and females.
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