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This study examined this question by assessing the influences of PTSD, <jats:italic>APOE<\/jats:italic> \u03b54 genotypes, DNA methylation, and other variables on the age- and dementia-associated biomarkers A\u03b240, A\u03b242, GFAP, NfL, and pTau-181 measured in plasma. Our primary hypothesis was that PTSD would be associated with elevated levels of these markers.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Analyses were based on data from a PTSD-enriched cohort of 849 individuals. We began by performing factor analyses of the biomarkers, the results of which identified a two-factor solution. Drawing from the ATN research framework, we termed the first factor, defined by A\u03b240 and A\u03b242, \u201cFactor A\u201d and the second factor, defined by GFAP, NfL and pTau-181, \u201cFactor TN.\u201d Next, we performed epigenome-wide association analyses (EWAS) of the two-factor scores. Finally, using structural equation modeling (SEM), we evaluated (a) the influence of PTSD, age, <jats:italic>APOE<\/jats:italic> \u03b54 genotype and other covariates on levels of the ATN factors, and (b) tested the mediating influence of the EWAS-significant DNAm loci on these associations.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The Factor A EWAS identified one significant locus, <jats:italic>cg13053408<\/jats:italic>, in <jats:italic>FANCD2OS<\/jats:italic>. The Factor TN analysis identified 3 EWAS-significant associations: <jats:italic>cg26033520<\/jats:italic> near <jats:italic>ASCC1, cg23156469<\/jats:italic> in <jats:italic>FAM20B,<\/jats:italic> and <jats:italic>cg15356923<\/jats:italic> in <jats:italic>FAM19A4<\/jats:italic>. The SEM showed age to be related to both factors, more so with Factor TN (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.581, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) than Factor A (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.330, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Genotype-determined African ancestry was associated with lower Factor A (<jats:italic>\u03b2<\/jats:italic>\u2009=\u20090.196, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Contrary to our primary hypothesis, we found a modest negative bivariate correlation between PTSD and the TN factor scores (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2212\u00a00.133, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) attributable primarily to reduced levels of GFAP (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2212\u00a00.128, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study identified novel epigenetic associations with ATN biomarkers and demonstrated robust age and ancestral associations that will be essential to consider in future efforts to develop the clinical applications of these tests. The association between PTSD and reduced GFAP, which has been reported previously, warrants further investigation.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13148-024-01649-3","type":"journal-article","created":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T10:01:54Z","timestamp":1709373714000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["An EWAS of dementia biomarkers and their associations with age, African ancestry, and PTSD"],"prefix":"10.1186","volume":"16","author":[{"given":"Mark W.","family":"Miller","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika J.","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark W.","family":"Logue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sage E.","family":"Hawn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,3,2]]},"reference":[{"issue":"4","key":"1649_CR1","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.3233\/JAD-210094","volume":"82","author":"KH Franks","year":"2021","unstructured":"Franks KH, Bransby L, Saling MM, Pase MP. 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