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With the exception of coding variants in <jats:italic>ADH1B<\/jats:italic> and <jats:italic>ALDH2<\/jats:italic>, little is known about the molecular effects of AUD\u2010associated loci. We previously reported that the AUD\u2010associated synonymous polymorphism rs279858 within the GABA<jats:sub>A<\/jats:sub> \u03b12 receptor subunit gene, <jats:italic>GABRA2<\/jats:italic>, was associated with gene expression of the chr4p12 GABA<jats:sub>A<\/jats:sub> subunit gene cluster in induced pluripotent stem cell (iPSC)\u2010derived neural cultures. Based on this and other studies that showed changes in <jats:italic>GABRA2<\/jats:italic> DNA methylation associated with schizophrenia and aging, we examined methylation in <jats:italic>GABRA2<\/jats:italic>. Specifically, using 69 iPSC lines and neural cultures derived from 47 of them, we examined whether <jats:italic>GABRA2<\/jats:italic> rs279858 genotype predicted methylation levels and whether methylation was related to GABA<jats:sub>A<\/jats:sub> receptor subunit gene expression. We found that the <jats:italic>GABRA2<\/jats:italic> CpG island undergoes random stochastic methylation during reprogramming and that methylation is associated with decreased <jats:italic>GABRA2<\/jats:italic> gene expression, an effect that extends to the <jats:italic>GABRB1<\/jats:italic> gene over 600\u2009kb distal to <jats:italic>GABRA2<\/jats:italic>. Further, we identified additive effects of <jats:italic>GABRA2<\/jats:italic> CpG methylation and <jats:italic>GABRA2<\/jats:italic> rs279858 genotype on expression of the <jats:italic>GABRB1<\/jats:italic> subunit gene in iPSC\u2010derived neural cultures.<\/jats:p>","DOI":"10.1002\/ajmg.b.32824","type":"journal-article","created":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T07:05:44Z","timestamp":1602140744000},"page":"464-474","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Induced pluripotent stem cell reprogramming\u2010associated methylation at the <scp><i>GABRA2<\/i><\/scp> promoter and chr4p12 <scp>GABA<sub>A<\/sub><\/scp> subunit gene expression in the context of alcohol use disorder"],"prefix":"10.1002","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5849-3336","authenticated-orcid":false,"given":"Alexandra","family":"Goetjen","sequence":"first","affiliation":[{"name":"Alcohol Research Center, Department of Psychiatry University of Connecticut School of Medicine  Farmington Connecticut USA"},{"name":"Genetics and Developmental Biology Graduate Program University of Connecticut School of Medicine  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maegan","family":"Watson","sequence":"additional","affiliation":[{"name":"Alcohol Research Center, Department of Psychiatry University of Connecticut School of Medicine  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Lieberman","sequence":"additional","affiliation":[{"name":"Alcohol Research Center, Department of Psychiatry University of Connecticut School of Medicine  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin","family":"Clinton","sequence":"additional","affiliation":[{"name":"Alcohol Research Center, Department of Psychiatry University of Connecticut School of Medicine  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry R.","family":"Kranzler","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry Perelman School of Medicine of the University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"VISN 4 MIRECC, Crescenz VAMC  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3616-0431","authenticated-orcid":false,"given":"Jonathan","family":"Covault","sequence":"additional","affiliation":[{"name":"Alcohol Research Center, Department of Psychiatry University of Connecticut School of Medicine  Farmington Connecticut USA"},{"name":"Institute for Systems Genomics University of Connecticut  Storrs Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,7]]},"reference":[{"issue":"2","key":"e_1_2_9_2_1","first-page":"291","article-title":"International Union of Pharmacology. 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