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Shared genetic etiology underlying late‐onset Alzheimer's disease and posttraumatic stress syndrome
Author(s) -
Lutz Michael W.,
Luo Sheng,
Williamson Douglas E.,
ChibaFalek Ornit
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.12128
Subject(s) - genome wide association study , genetic load , etiology , genetic association , pleiotropy , disease , posttraumatic stress , dementia , biology , medicine , single nucleotide polymorphism , genetics , clinical psychology , gene , psychiatry , population , genotype , phenotype , environmental health , inbreeding
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.