title: Genome-wide analyses of aggressiveness in attention-deficit hyperactivity disorder.
abstract: Aggressiveness is a behavioral trait that has the potential to be harmful to individuals and society. With an estimated heritability of about 40%, genetics is important in its development. We performed an exploratory genome-wide association (GWA) analysis of childhood aggressiveness in attention deficit hyperactivity disorder (ADHD) to gain insight into the underlying biological processes associated with this trait. Our primary sample consisted of 1,060 adult ADHD patients (aADHD). To further explore the genetic architecture of childhood aggressiveness, we performed enrichment analyses of suggestive genome-wide associations observed in aADHD among GWA signals of dimensions of oppositionality (defiant/vindictive and irritable dimensions) in childhood ADHD (cADHD). No single polymorphism reached genome-wide significance (P < 5.00E-08). The strongest signal in aADHD was observed at rs10826548, within a long noncoding RNA gene (beta = -1.66, standard error (SE) = 0.34, P = 1.07E-06), closely followed by rs35974940 in the neurotrimin gene (beta = 3.23, SE = 0.67, P = 1.26E-06). The top GWA SNPs observed in aADHD showed significant enrichment of signals from both the defiant/vindictive dimension (Fisher's P-value = 2.28E-06) and the irritable dimension in cADHD (Fisher's P-value = 0.0061). In sum, our results identify a number of biologically interesting markers possibly underlying childhood aggressiveness and provide targets for further genetic exploration of aggressiveness across psychiatric disorders. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.
authors.affiliation: Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.|K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway.|Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
authors.forename: Erlend J
authors.initials: EJ
authors.lastname: Brevik
authors.affiliation: Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Marjolein M J
authors.initials: MM
authors.lastname: van Donkelaar
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Frankfurt, Frankfurt, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Weber
authors.affiliation: Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.|Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.|Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sánchez-Mora
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinik Nürtingen, Nürtingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Jacob
authors.affiliation: Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Rivero
authors.affiliation: Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kittel-Schneider
authors.affiliation: Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.|Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Iris
authors.initials: I
authors.lastname: Garcia-Martínez
authors.affiliation: Department of Forensic Psychiatry, Child and Youth Forensic Service, University Hospital of Psychiatry, Zurich, Switzerland.|Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Aebi
authors.affiliation: Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Kimm
authors.initials: K
authors.lastname: van Hulzen
authors.affiliation: Facultat de Biologia, Departament de Genètica, Universitat de Barcelona, Catalonia, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain.|Institut de Biomedicina de la Universitat de Barcelona (IBUB), Catalonia, Spain.
authors.forename: Bru
authors.initials: B
authors.lastname: Cormand
authors.affiliation: Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.|Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.|Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain.|Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Josep A
authors.initials: JA
authors.lastname: Ramos-Quiroga
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinik Nürtingen, Nürtingen, Germany.|Department of Translational Neuroscience, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, The Netherlands.
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Lesch
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Frankfurt, Frankfurt, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.affiliation: Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.|Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.|Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Ribasés
authors.affiliation: Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.affiliation: Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.|K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Maj-Britt
authors.initials: MB
authors.lastname: Posserud
authors.affiliation: Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.|Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Stefan
authors.initials: S
authors.lastname: Johansson
authors.affiliation: K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway.|Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
authors.forename: Astri J
authors.initials: AJ
authors.lastname: Lundervold
authors.affiliation: Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.|K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Jan
authors.initials: J
authors.lastname: Haavik
authors.affiliation: K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway.
authors.forename: Tetyana
authors.initials: T
authors.lastname: Zayats
mesh_terms: D000293:Adolescent; D000328:Adult; D000374:Aggression / Q000502:physiology* / Q000523:psychology; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000235:genetics* / Q000523:psychology; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
keywords: ADHD; GWAS; aggression