Shared genetic etiology underlying late-onset Alzheimer's disease and posttraumatic stress syndrome.
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.
Type
Journal articleSubject
MS4A gene familyPTSD
genetic pleiotropy
inflammation and immune-based pathways and Alzheimer's disease
late-onset Alzheimer's disease
posttraumatic stress disorder
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https://hdl.handle.net/10161/21106Published Version (Please cite this version)
10.1002/alz.12128Publication Info
Lutz, Michael W; Luo, Sheng; Williamson, Douglas E; & Chiba-Falek, Ornit (2020). Shared genetic etiology underlying late-onset Alzheimer's disease and posttraumatic
stress syndrome. Alzheimers Dement. 10.1002/alz.12128. Retrieved from https://hdl.handle.net/10161/21106.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Ornit Chiba-Falek
Professor in Neurology
Functional genomics Non-coding regulatory variants in the human genome Genetics of
complex neurological diseases
Sheng Luo
Professor of Biostatistics & Bioinformatics
Michael William Lutz
Associate Professor in Neurology
Developing and using computational biology methods to understand the genetic basis
of disease with a focus on Alzheimer’s Disease. Recent work has focused on identification
and validation of clinically-relevant biomarkers for Alzheimer’s disease and Alzheimer’s
disease with Lewy bodies.
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