title: Rigorous tests of gene-environment interactions in a lab study of the oxytocin receptor gene (OXTR), alcohol exposure, and aggression.
abstract: Naturalistic studies of gene-environment interactions (G X E) have been plagued by several limitations, including difficulty isolating specific environmental risk factors from other correlated aspects of the environment, gene-environment correlation (rGE ), and the use of a single genetic variant to represent the influence of a gene. We present results from 235 Finnish young men in two lab studies of aggression and alcohol challenge that attempt to redress these limitations of the extant G X E literature. Specifically, we use a latent variable modeling approach in an attempt to more fully account for genetic variation across the oxytocin receptor gene (OXTR) and to robustly test its main effects on aggression and its interaction with alcohol exposure. We also modeled aggression as a latent variable comprising various indices, including the average and maximum levels of aggression, the earliest trial on which aggression was expressed, and the proportion of trials on which the minimum and maximum levels of aggression were expressed. The best fitting model for the genetic variation across OXTR included six factors derived from an exploratory factor analysis, roughly corresponding to six haplotype blocks. Aggression levels were higher on trials in which participants were administered alcohol, won, or were provoked. There was a significant main effect of OXTR on aggression across studies after controlling for covariates. The interaction of OXTR and alcohol was also significant across studies, such that OXTR had stronger effects on aggression in the alcohol administration condition. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Psychology Department, Emory University, Atlanta, Georgia.
authors.forename: Devon
authors.initials: D
authors.lastname: LoParo
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Department of Psychology and Logopedics, Abo Akademi University, Turku, Finland.
authors.forename: Ada
authors.initials: A
authors.lastname: Johansson
authors.affiliation: Psychology Department, Emory University, Atlanta, Georgia.|Center for Translational Social Neuroscience, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia.
authors.forename: Hasse
authors.initials: H
authors.lastname: Walum
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Westberg
authors.affiliation: Department of Psychology and Logopedics, Abo Akademi University, Turku, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Santtila
authors.affiliation: Psychology Department, Emory University, Atlanta, Georgia.
authors.forename: Irwin
authors.initials: I
authors.lastname: Waldman
mesh_terms: D000293:Adolescent; D000328:Adult; D000374:Aggression / Q000187:drug effects*; D000428:Alcohol Drinking / Q000523:psychology; D000483:Alleles; D000431:Ethanol / Q000009:adverse effects*; D005387:Finland; D059647:Gene-Environment Interaction; D014644:Genetic Variation / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D010121:Oxytocin / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018045:Receptors, Oxytocin / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D055815:Young Adult
chemical_list: D018045:Receptors, Oxytocin; D000431:Ethanol; D010121:Oxytocin
keywords: aggression; alcohol; oxytocin