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In this study, we investigated the effects of 2 <jats:styled-content style=\"fixed-case\">AUD<\/jats:styled-content>\u2010risk\u2010associated single nucleotide polymorphisms, <jats:italic><jats:styled-content style=\"fixed-case\">GABRA<\/jats:styled-content>2<\/jats:italic> rs279858 and <jats:italic><jats:styled-content style=\"fixed-case\">GRIK<\/jats:styled-content>1<\/jats:italic> rs2832407, on the subjective response to alcohol administered intravenously to healthy social drinkers in a laboratory setting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In total, 93 self\u2010identified European American social drinkers underwent 3 blinded laboratory sessions in which they received intravenous infusions of ethanol at 3 target blood alcohol levels (0.00\u00a0mg%, 40\u00a0mg%, and 100\u00a0mg%) using a \u201cclamp\u201d procedure. The self\u2010reported Biphasic Alcohol Effects Scale (<jats:styled-content style=\"fixed-case\">BAES<\/jats:styled-content>) stimulation and sedation subscales were the primary outcome measures. We examined the effects of these 2 genetic variants on subjective response to alcohol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>For the <jats:styled-content style=\"fixed-case\">BAES<\/jats:styled-content> stimulation subscale scores, adjusting for age, baseline scores, and time effects, individuals with 2 copies of the <jats:italic><jats:styled-content style=\"fixed-case\">GABRA<\/jats:styled-content>2<\/jats:italic> rs279858 C \u201crisk\u201d allele for <jats:styled-content style=\"fixed-case\">AUD<\/jats:styled-content> exhibited the greatest stimulant responses to high\u2010dose alcohol compared to the other risk allele counts (dose\u2010by\u2010allele count interaction effect, <jats:italic>p\u00a0<\/jats:italic>=\u00a00.001, post hoc contrast for C\u2010allele, <jats:italic>p\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.012). For the <jats:styled-content style=\"fixed-case\">BAES<\/jats:styled-content> sedation subscale scores, adjusting for the same covariates, we detected a dose\u2010by\u2010allele count interaction effect (<jats:italic>p\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.0044) such that subjects with 2 copies of the <jats:italic><jats:styled-content style=\"fixed-case\">GRIK<\/jats:styled-content>1<\/jats:italic> C \u201crisk\u201d allele reported the greatest sedative response to the higher alcohol dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study suggests that gene variants contributing to the risk for <jats:styled-content style=\"fixed-case\">AUD<\/jats:styled-content> may alter features of the alcohol dose\u2013response relationship in specific ways. <jats:italic><jats:styled-content style=\"fixed-case\">GABRA<\/jats:styled-content>2<\/jats:italic> rs279858*C enhances stimulant responses to higher levels of alcohol, while the <jats:italic><jats:styled-content style=\"fixed-case\">GRIK<\/jats:styled-content>1<\/jats:italic> rs2832407*C\u2010allele increases sedative responses. In summary, <jats:italic><jats:styled-content style=\"fixed-case\">GRIK<\/jats:styled-content>1<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">GABRA<\/jats:styled-content>2<\/jats:italic> variants have distinct effects on the dose\u2010related subjective response to intravenous alcohol in humans.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13516","type":"journal-article","created":{"date-parts":[[2017,11,13]],"date-time":"2017-11-13T15:02:39Z","timestamp":1510585359000},"page":"2025-2032","source":"Crossref","is-referenced-by-count":14,"title":["<i><scp>GRIK<\/scp>1<\/i> and <i><scp>GABRA<\/scp>2<\/i> Variants Have Distinct Effects on the Dose\u2010Related Subjective Response to Intravenous Alcohol in Healthy Social Drinkers"],"prefix":"10.1111","volume":"41","author":[{"given":"Bao\u2010Zhu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine New Haven Connecticut"},{"name":"Department of Veterans Affairs Alcohol Research Center VA Connecticut Healthcare System (116\u2010A) West Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert J.","family":"Arias","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine New Haven Connecticut"},{"name":"Department of Veterans Affairs Alcohol Research Center VA Connecticut Healthcare System (116\u2010A) West Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Feinn","sequence":"additional","affiliation":[{"name":"Quinnipiac University Hamden Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Krystal","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine New Haven Connecticut"},{"name":"Department of Veterans Affairs Alcohol Research Center VA Connecticut Healthcare System (116\u2010A) West Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Gelernter","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine New Haven Connecticut"},{"name":"Department of Veterans Affairs Alcohol Research Center VA Connecticut Healthcare System (116\u2010A) West Haven Connecticut"},{"name":"Departments of Genetics and Neuroscience Yale University School of Medicine New Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismene L.","family":"Petrakis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale University School of Medicine New Haven Connecticut"},{"name":"Department of Veterans Affairs Alcohol Research Center VA Connecticut Healthcare System (116\u2010A) West Haven Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agt163"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3758\/BF03192707"},{"key":"e_1_2_7_4_1","unstructured":"2002 John Wiley & Sons Inc. 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