{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:37:18Z","timestamp":1792816638457,"version":"4.5.0"},"reference-count":61,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:00:00Z","timestamp":1792713600000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R01 AA026658"],"award-info":[{"award-number":["R01 AA026658"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["17282"],"award-info":[{"award-number":["17282"]}],"id":[{"id":"10.13039\/501100003246","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":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Variation in gene expression is hypothesized to be a major source of phenotypic variation underlying the liability for alcohol misuse.\n \n Caenorhabditis elegans<\/jats:italic>\n <\/jats:styled-content>\n (\n \n C. elegans<\/jats:italic>\n <\/jats:styled-content>\n ) has proven to be a valuable model in the identification of genes that modify behavioral responses to alcohol. Genetic variation in wild strains represents allelic differences that are tolerated by natural selection pressures and, therefore, are more likely to model the allelic differences that are present in humans compared with laboratory\u2010generated mutations.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We examined the influence of natural alleles on gene expression in response to ethanol by mapping eQTL in\n \n C. elegans<\/jats:italic>\n <\/jats:styled-content>\n . We used a recombinant inbred panel derived from four wild strains to examine the regulation of ethanol exposure\u2010induced gene expression. We performed differential gene expression analyses and mapped eQTL. Detailed examination of\n trans\u2010<\/jats:italic>\n band\n ChrV\u20100:3 Mb<\/jats:sub>\n included quantification of the behavioral responses to ethanol for top candidate genes in the\n trans<\/jats:italic>\n \u2010band.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Ethanol exposure increased\n trans\u2010<\/jats:italic>\n eQTL and decreased\n cis\u2010<\/jats:italic>\n eQTL. We observed the largest shift in distantly regulated transcripts on the first three Mb on chromosome V that contained 355\n trans\u2010<\/jats:italic>\n eQTL in a single\n trans\u2010<\/jats:italic>\n band. The eQTL group in this\n trans\u2010<\/jats:italic>\n band was involved in processes implicated in alcohol use disorder and its gene ontology terms included unsaturated fatty acids, responses to stress and environment, and immune and defense responses. We validated this genomic region using an introgression line and identified\n nhr\u2010131<\/jats:italic>\n and\n dod\u201019<\/jats:italic>\n as potential polymorphic modifiers of\n trans\u2010<\/jats:italic>\n band\n ChrV\u20100:3 Mb<\/jats:sub>\n . We tested null mutations in\n nhr\u2010131<\/jats:italic>\n and\n dod\u201019<\/jats:italic>\n and found that\n dod\u201019<\/jats:italic>\n is required for the normal development of acute functional tolerance (AFT) to ethanol.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Natural genetic variation in these wild strains primarily affected\n trans<\/jats:italic>\n \u2010regulated gene expression. Examination of\n trans\u2010<\/jats:italic>\n band\n ChrV\u20100:3 Mb<\/jats:sub>\n identified\n dod\u201019<\/jats:italic>\n as a candidate expression modifier gene that regulates the development of AFT to ethanol and further implicates membrane biology in this process.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/acer.70432","type":"journal-article","created":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:57:12Z","timestamp":1792814232000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Expression Profiling of a Recombinant Inbred Line Panel Identifies the\n dod\u201019<\/i>\n Gene as a Regulator of Ethanol Response Behaviors in\n \n C. elegans<\/i>\n <\/scp>"],"prefix":"10.1111","volume":"50","author":[{"given":"Marijke H.","family":"van Wijk","sequence":"first","affiliation":[{"name":"Laboratory of Nematology Wageningen University Wageningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark G.","family":"Sterken","sequence":"additional","affiliation":[{"name":"Laboratory of Nematology Wageningen University Wageningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth C.","family":"Quamme","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost A. G.","family":"Riksen","sequence":"additional","affiliation":[{"name":"Laboratory of Nematology Wageningen University Wageningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5321-2996","authenticated-orcid":false,"given":"Basten L.","family":"Snoek","sequence":"additional","affiliation":[{"name":"Theoretical Biology and Bioinformatics Utrecht University Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3028-3219","authenticated-orcid":false,"given":"Stefan J. S.","family":"van de Ruitenbeek","sequence":"additional","affiliation":[{"name":"Laboratory of Nematology Wageningen University Wageningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2749-6531","authenticated-orcid":false,"given":"Laura D.","family":"Mathies","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University Richmond Virginia USA"},{"name":"Virginia Commonwealth University Alcohol Research Center Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2976-2653","authenticated-orcid":false,"given":"Andrew G.","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University Richmond Virginia USA"},{"name":"Virginia Commonwealth University Alcohol Research Center Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9002-5361","authenticated-orcid":false,"given":"Jill C.","family":"Bettinger","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Virginia Commonwealth University Richmond Virginia USA"},{"name":"Virginia Commonwealth University Alcohol Research Center Richmond Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4822-4436","authenticated-orcid":false,"given":"Jan E.","family":"Kammenga","sequence":"additional","affiliation":[{"name":"Laboratory of Nematology Wageningen University Wageningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1111\/acer.13362","article-title":"Genomewide Association Study of Alcohol Dependence Identifies Risk Loci Altering Ethanol\u2010Response Behaviors in Model Organisms","volume":"41","author":"Adkins A. 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