dc.contributor.author	Lutz, Michael W
dc.contributor.author	Luo, Sheng
dc.contributor.author	Williamson, Douglas E
dc.contributor.author	Chiba-Falek, Ornit
dc.date.accessioned	2020-07-01T13:56:15Z
dc.date.available	2020-07-01T13:56:15Z
dc.date.issued	2020-06-26
dc.date.updated	2020-07-01T13:56:10Z
dc.description.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.
dc.identifier.issn	1552-5260
dc.identifier.issn	1552-5279
dc.identifier.uri	https://hdl.handle.net/10161/21106
dc.language	eng
dc.publisher	Wiley
dc.relation.ispartof	Alzheimers Dement
dc.relation.isversionof	10.1002/alz.12128
dc.subject	MS4A gene family
dc.subject	PTSD
dc.subject	genetic pleiotropy
dc.subject	inflammation and immune-based pathways and Alzheimer's disease
dc.subject	late-onset Alzheimer's disease
dc.subject	posttraumatic stress disorder
dc.title	Shared genetic etiology underlying late-onset Alzheimer's disease and posttraumatic stress syndrome.
dc.type	Journal article
duke.contributor.orcid	Lutz, Michael W\|0000-0001-8809-5574
duke.contributor.orcid	Luo, Sheng\|0000-0003-4214-5809
duke.contributor.orcid	Chiba-Falek, Ornit\|0000-0002-2529-8785
pubs.organisational-group	School of Medicine
pubs.organisational-group	Duke Science & Society
pubs.organisational-group	Pathology
pubs.organisational-group	Neurology, Behavioral Neurology
pubs.organisational-group	Duke
pubs.organisational-group	Initiatives
pubs.organisational-group	Institutes and Provost's Academic Units
pubs.organisational-group	Clinical Science Departments
pubs.organisational-group	Neurology
pubs.organisational-group	Duke Clinical Research Institute
pubs.organisational-group	Biostatistics & Bioinformatics
pubs.organisational-group	Institutes and Centers
pubs.organisational-group	Basic Science Departments
pubs.publication-status	Published online

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

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