Shared genetic etiology underlying late-onset Alzheimer's disease and posttraumatic stress syndrome

Michael W. Lutz, Sheng Luo, Douglas E. Williamson, Ornit Chiba-Falek

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Introduction: Late-onset Alzheimer's disease (LOAD) manifests comorbid neuropsychiatric symptoms and posttraumatic stress disorder (PTSD) is associated with an increased risk for dementia in late life, suggesting the two disorders may share genetic etiologies. Methods: We performed genetic pleiotropy analysis using LOAD and PTSD genome-wide association study (GWAS) datasets from white and African-American populations, followed by functional-genomic analyses. Results: We found an enrichment for LOAD across increasingly stringent levels of significance with the PTSD GWAS association (LOAD|PTSD) in the discovery and replication cohorts and a modest enrichment for the reverse conditional association (PTSD|LOAD). LOAD|PTSD association analysis identified and replicated the MS4A genes region. These genes showed similar expression pattern in brain regions affected in LOAD, and across-brain-tissue analysis identified a significant association for MS4A6A. The African-American samples showed moderate enrichment; however, no false discovery rate–significant associations. Discussion: We demonstrated common genetic signatures for LOAD and PTSD and suggested immune response as a common pathway for these diseases.

Original languageEnglish (US)
Pages (from-to)1280-1292
Number of pages13
JournalAlzheimer's and Dementia
Volume16
Issue number9
DOIs
StatePublished - Sep 1 2020
Externally publishedYes

Keywords

  • genetic pleiotropy
  • inflammation and immune-based pathways and Alzheimer's disease
  • late-onset Alzheimer's disease
  • MS4A gene family
  • posttraumatic stress disorder
  • PTSD

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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