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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Lutz, MW; Luo, S; Williamson, DE; Chiba-Falek, O

Published Date

  • September 2020

Published In

Volume / Issue

  • 16 / 9

Start / End Page

  • 1280 - 1292

PubMed ID

  • 32588970

Pubmed Central ID

  • PMC7769164

Electronic International Standard Serial Number (EISSN)

  • 1552-5279

Digital Object Identifier (DOI)

  • 10.1002/alz.12128


  • eng

Conference Location

  • United States