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Although the epigenomic literature on smoking is well established, studies evaluating the role of epigenetics in ND are limited. In this study, we examined the epigenomic signatures of ND and how these differ from smoking exposure to identify biomarkers specific to ND. We investigated the peripheral epigenetic profile of smoking status (SS) and ND in a US male veteran cohort. DNA from saliva was collected from 1135 European American (EA) male US military veterans. DNAm was assessed using the Illumina Infinium Human MethylationEPIC BeadChip array. SS was evaluated as current smokers (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009137; 12.1%) and non\u2010current smokers (never and former;\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009998; 87.9%). ND\n                    <jats:sub>FTND<\/jats:sub>\n                    was assessed as a continuous variable using the Fagerstr\u00f6m Test for ND (FTND;\n                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u20091135; mean\u2009=\u20092.54\u2009\u00b1\u20092.29). Epigenome\u2010wide association studies (EWAS) and co\u2010methylation analyses were conducted for SS and ND\n                    <jats:sub>FTND<\/jats:sub>\n                    . A total of 450 and 22 genome\u2010wide significant differentially methylated sites (DMS) were associated with SS and ND\n                    <jats:sub>FTND<\/jats:sub>\n                    , respectively (15 overlapped DMS). We identified 97 DMS (43 genes) in SS\u2010EWAS previously reported in the literature, including\n                    <jats:italic>AHRR<\/jats:italic>\n                    and\n                    <jats:italic>F2RL3<\/jats:italic>\n                    genes (\n                    <jats:italic>p<\/jats:italic>\n                    \u2010value: 1.95\u2009\u00d7\u200910\n                    <jats:sup>\u221283<\/jats:sup>\n                    to 4.55\u2009\u00d7\u200910\n                    <jats:sup>\u221233<\/jats:sup>\n                    ). ND\n                    <jats:sub>FTND<\/jats:sub>\n                    novel DMS mapped to\n                    <jats:italic>NEUROG1<\/jats:italic>\n                    ,\n                    <jats:italic>ANPEP<\/jats:italic>\n                    , and\n                    <jats:italic>SLC29A1<\/jats:italic>\n                    . Co\u2010methylation analysis identified 386 modules (11 SS\u2010related and 19 ND\n                    <jats:sub>FTND<\/jats:sub>\n                    \u2010related). SS\u2010related modules showed enrichment for alcoholism, while ND\n                    <jats:sub>FTND<\/jats:sub>\n                    \u2010related modules were enriched for nicotine addiction. This study confirms previous findings associated with SS and identifies novel and\u2014potentially specific\u2014epigenetic biomarkers of ND that may inform prognosis and novel treatment strategies.\n                  <\/jats:p>","DOI":"10.1111\/adb.13259","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T23:43:13Z","timestamp":1669851793000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dissecting the epigenomic differences between smoking and nicotine dependence in a veteran cohort"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4986-5094","authenticated-orcid":false,"given":"Sheila Tiemi","family":"Nagamatsu","sequence":"first","affiliation":[{"name":"Division of Human Genetics, Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"},{"name":"VA CT Healthcare Center  West Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert H.","family":"Pietrzak","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"},{"name":"VA CT Healthcare Center  West Haven Connecticut USA"},{"name":"Clinical Neurosciences Division U.S. Department of Veterans Affairs National Center of Posttraumatic Stress Disorder  West Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6472-7052","authenticated-orcid":false,"given":"Ke","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"},{"name":"VA CT Healthcare Center  West Haven Connecticut USA"},{"name":"Clinical Neurosciences Division U.S. Department of Veterans Affairs National Center of Posttraumatic Stress Disorder  West Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John H.","family":"Krystal","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"},{"name":"VA CT Healthcare Center  West Haven Connecticut USA"},{"name":"Clinical Neurosciences Division U.S. Department of Veterans Affairs National Center of Posttraumatic Stress Disorder  West Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4067-1859","authenticated-orcid":false,"given":"Joel","family":"Gelernter","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"},{"name":"VA CT Healthcare Center  West Haven Connecticut USA"},{"name":"Clinical Neurosciences Division U.S. Department of Veterans Affairs National Center of Posttraumatic Stress Disorder  West Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janitza Liz","family":"Montalvo\u2010Ortiz","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Department of Psychiatry Yale University School of Medicine  New Haven Connecticut USA"},{"name":"VA CT Healthcare Center  West Haven Connecticut USA"},{"name":"Clinical Neurosciences Division U.S. Department of Veterans Affairs National Center of Posttraumatic Stress Disorder  West Haven Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,11,30]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Global Report on Trends in Prevalence of Tobacco Smoking 2000\u20132025","author":"WHO","year":"2018"},{"key":"e_1_2_9_3_1","unstructured":"CDC.Current cigarette smoking among adults in the United States. 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