{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T03:33:32Z","timestamp":1763782412644,"version":"3.45.0"},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008478","name":"Wake Forest School of Medicine","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100008478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AA028007","AA019431"],"award-info":[{"award-number":["AA028007","AA019431"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcohol, Clinical and Experimental Research"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Consumed ethanol is primarily metabolized by the liver, with resulting products of ethanol metabolism, acetaldehyde and salsolinol that influence brain activity and alcohol drinking behavior. Alcohol consumption in humans is highly heritable with numerous associated genetic variants. Functional variants in the\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>ADH<\/jats:italic>\n                      <\/jats:styled-content>\n                      and\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>ALDH<\/jats:italic>\n                      <\/jats:styled-content>\n                      genes influence liver alcohol metabolism but only account for a small percentage of variance in consumption. We hypothesized that variation in hepatic molecular networks during the induction phase, where animals consume identical amounts of alcohol, predicted variation in drinking behavior during subsequent ad\u00a0libitum access in nonhuman primates (\n                      <jats:styled-content style=\"fixed-case\">NHPs<\/jats:styled-content>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We studied male rhesus macaques at baseline and during the uniform consumption phase that became discordant at the later ad\u00a0libitum phase. The study design increased the likelihood of identifying functional molecular differences between light drinkers (\n                      <jats:styled-content style=\"fixed-case\">LD<\/jats:styled-content>\n                      ) and very heavy drinkers (\n                      <jats:styled-content style=\"fixed-case\">VHD<\/jats:styled-content>\n                      ) before animals exhibited differences in drinking behavior. We analyzed liver biopsies, provided by the Monkey Alcohol and Tissue Research Resource (\n                      <jats:styled-content style=\"fixed-case\">MATRR<\/jats:styled-content>\n                      ), collected at baseline and after 3\u2009months of uniform consumption, using multiomic and histologic methods.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found hepatic molecular pathways and networks differed between LD and VHD at baseline and in response to identical consumption. Notably, Sirtuin Signaling and a MYC\u2010regulated network were significantly enriched for differentially abundant molecules in both LD and VHD response to uniform alcohol consumption. Potential epigenomic mechanisms regulating response to alcohol consumption were significantly different with LD response primarily through microRNAs, and VHD primarily through DNA methylation. Histological analysis of liver biopsies showed no liver pathologies in either group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings of differences in molecular networks prior to alcohol consumption suggest genetic variation contributes to drinking phenotypes, and differences in molecular response to uniform alcohol consumption suggest epigenetic mechanisms regulating liver networks also contribute to the development and progression of drinking phenotypes in NHP.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acer.70162","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T12:14:07Z","timestamp":1758197647000},"page":"2470-2484","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Liver molecular networks associated with drinking behavior in nonhuman primates"],"prefix":"10.1111","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8836-3783","authenticated-orcid":false,"given":"Laura A.","family":"Cox","sequence":"first","affiliation":[{"name":"Center for Precision Medicine Wake Forest University School of Medicine  Winston\u2010Salem North Carolina USA"},{"name":"Section on Molecular Medicine, Department of Internal Medicine Wake Forest University School of Medicine  Winston\u2010Salem North Carolina USA"},{"name":"Section on Comparative Medicine, Department of Pathology Wake Forest University School of Medicine  Winston\u2010Salem North Carolina USA"},{"name":"Southwest National Primate Research Center Texas Biomedical Research Institute  San Antonio Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James B.","family":"Daunais","sequence":"additional","affiliation":[{"name":"Center for Precision Medicine Wake Forest University School of Medicine  Winston\u2010Salem North Carolina 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A.","family":"Grant","sequence":"additional","affiliation":[{"name":"Oregon National Primate Research Center Oregon Health Sciences University  Portland Oregon USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Olivier","sequence":"additional","affiliation":[{"name":"Center for Precision Medicine Wake Forest University School of Medicine  Winston\u2010Salem North Carolina USA"},{"name":"Section on Molecular Medicine, Department of Internal Medicine Wake Forest University School of Medicine  Winston\u2010Salem North Carolina 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