title: Drinking beyond a lifetime: New and emerging insights into paternal alcohol exposure on subsequent generations.
abstract: Alcohol-use disorder (AUD) is prevalent and associated with substantial socioeconomic costs. While heritability estimates of AUD are ∼50%, identifying specific gene variants associated with risk for AUD has proven challenging despite considerable investment. Emerging research into heritability of complex diseases has implicated transmission of epigenetic variants in the development of behavioral phenotypes, including drug preference and drug-induced behavior. Several recent rodent studies have specifically focused on paternal transmission of epigenetic variants, which is especially relevant because sires are not present for offspring rearing and changes to offspring phenotype are assumed to result from modifications to the sperm epigenome. While considerable interest in paternal transmission of epigenetic variants has emerged recently, paternal alcohol exposures have been studied for 30+ years with interesting behavioral and physiologic effects noted on offspring. However, only recently, with improvements in technology to identify epigenetic modifications in germ cells, has it been possible to identify mechanisms by which paternal ethanol exposure alters offspring behavior. This review presents an overview of epigenetic inheritance in the context of paternal ethanol exposure and suggests future studies to identify specific effects of paternal ethanol exposure on offspring behavior and response to ethanol.
authors.affiliation: Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Andrey
authors.initials: A
authors.lastname: Finegersh
authors.affiliation: Center for Neuroscience, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Rompala
authors.affiliation: Children's Hospital of Oakland Research Institute, Oakland, CA, USA.
authors.forename: David I K
authors.initials: DI
authors.lastname: Martin
authors.affiliation: Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: homanicsge@anes.upmc.edu.
authors.forename: Gregg E
authors.initials: GE
authors.lastname: Homanics
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics*; D000437:Alcoholism / Q000235:genetics*; D000818:Animals; D016241:Child of Impaired Parents / Q000523:psychology*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D005220:Fathers; D006801:Humans; D008297:Male; D010641:Phenotype
keywords: Alcoholism; DNA methylation; Epigenetics; Histones; Transgenerational inheritance; ncRNAs