DNA methylation-wide association study of prevalent and incident dementia in the US Health and Retirement Study

Abstract BACKGROUND: Peripheral blood DNA methylation may have utility as an early dementia risk biomarker. METHODS: We analyzed DNA methylation (blood collected 2016) and cognitive impairment in the Health and Retirement Study, a longitudinal study representative of US adults over age 50 (3,921 individuals and 585,356 CpG sites). We analyzed methylation associations with cognitive status both cross-sectionally and prospectively among participants with normal cognition at baseline with four years follow-up. RESULTS: Cross-sectionally, 5,322 CpGs were associated (pvalue<0.01) with cognitive impairment non-dementia, and 14,366 (166 genome-wide FDR<0.05) with dementia. Prospectively, 4,898 CpGs were associated with any-impairment. Enriched biologic pathways include ion transport, ligand-gated channel, and neuron differentiation. Nine CpGs overlapped all analyses including cg02583484 (HNRNPA1), cg15266133 (LOC102724084), cg24287460 (CCDC48), cg17124509 (C17orf57), and cg02553054 (SMARCD1). DISCUSSION: CpGs identified were enriched in pathways related to Alzheimers disease pathology and provide promising grounds for non-invasive blood biomarkers. Future studies for replication and with longer follow up are needed.

• Publication year

  2025

• Venue

  medRxiv

• Publication date

  2025-11-13

• Fields of study

  Medicine

• Identifiers
  DOI 10.1101/2025.11.10.25339919PMID 41292628PMCID 12642722
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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