title: Polygenic Risk for Externalizing Psychopathology and Executive Dysfunction in Trauma-Exposed Veterans.
abstract: The frequent co-occurrence of antisocial behavior and other disinhibited phenotypes reflects a highly heritable externalizing spectrum. We examined the molecular genetic basis of this spectrum by testing polygenic associations with psychopathology symptoms, impulsive traits, and cognitive functions in two samples of primarily military veterans (n=537,n=194). We also investigated whether polygenic risk for externalizing moderated the effects of trauma on these phenotypes. As hypothesized, polygenic risk positively predicted externalizing psychopathology and negatively predicted performance on inhibitory control tasks. Gene-by-environment effects were also evident, with trauma exposure predicting greater impulsivity and less working memory capacity, but only at high levels of genetic liability. As expected, polygenic risk was not associated with internalizing psychopathology or episodic memory performance. This is the first independent replication of the polygenic score as a measure of genetic predispositions for externalizing and provides preliminary evidence that executive dysfunction is a heritable vulnerability for externalizing psychopathology.
authors.affiliation: National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System; Department of Psychiatry, Boston University School of Medicine.
authors.forename: Naomi
authors.initials: N
authors.lastname: Sadeh
authors.affiliation: National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System; Department of Psychiatry, Boston University School of Medicine.
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Wolf
authors.affiliation: Research Service, VA Boston Healthcare System, Boston, MA; Biomedical Genetics, Boston University School of Medicine, Boston, MA; Department of Biostatistics, Boston University School of Public Health.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Logue
authors.affiliation: National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System.
authors.forename: Joanna
authors.initials: J
authors.lastname: Lusk
authors.affiliation: National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System; Department of Psychiatry, Boston University School of Medicine.
authors.forename: Jasmeet P
authors.initials: JP
authors.lastname: Hayes
authors.affiliation: Translational Research Center for TBI and Stress Disorders and Geriatric Research, Educational and Clinical Center, VA Boston Healthcare System; Department of Psychiatry, Harvard Medical School.
authors.forename: Regina E
authors.initials: RE
authors.lastname: McGlinchey
authors.affiliation: Translational Research Center for TBI and Stress Disorders and Geriatric Research, Educational and Clinical Center, VA Boston Healthcare System; Department of Psychiatry, Harvard Medical School.
authors.forename: William P
authors.initials: WP
authors.lastname: Milberg
authors.affiliation: Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System.
authors.forename: Annjanette
authors.initials: A
authors.lastname: Stone
authors.affiliation: Pharmacogenomics Analysis Laboratory, Research Service, Central Arkansas Veterans Healthcare System.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Schichman
authors.affiliation: National Center for PTSD, Behavioral Science Division, VA Boston Healthcare System; Department of Psychiatry, Boston University School of Medicine.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Miller
keywords: genes; impulsivity; inhibitory control; internalizing; veterans; working memory