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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+Show Affiliations

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.Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.Department of Psychiatry, Psychosomatics and Psychotherapy, University of Frankfurt, Frankfurt, Germany.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 Psychotherapy, Klinik Nürtingen, Nürtingen, Germany.Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany.Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany.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.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.Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.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.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.No affiliation info availableDepartment of Psychiatry and Psychotherapy, Klinik Nürtingen, Nürtingen, Germany. Department of Translational Neuroscience, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, The Netherlands.Department of Psychiatry, Psychosomatics and Psychotherapy, University of Frankfurt, Frankfurt, Germany.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 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.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.Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway. Department of Clinical Science, University of Bergen, 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.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.K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

27021288

Citation

Brevik, Erlend J., et al. "Genome-wide Analyses of Aggressiveness in Attention-deficit Hyperactivity Disorder." American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics, vol. 171, no. 5, 2016, pp. 733-47.
Brevik EJ, van Donkelaar MM, Weber H, et al. Genome-wide analyses of aggressiveness in attention-deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet. 2016;171(5):733-47.
Brevik, E. J., van Donkelaar, M. M., Weber, H., Sánchez-Mora, C., Jacob, C., Rivero, O., ... Zayats, T. (2016). Genome-wide analyses of aggressiveness in attention-deficit hyperactivity disorder. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics, 171(5), pp. 733-47. doi:10.1002/ajmg.b.32434.
Brevik EJ, et al. Genome-wide Analyses of Aggressiveness in Attention-deficit Hyperactivity Disorder. Am J Med Genet B Neuropsychiatr Genet. 2016;171(5):733-47. PubMed PMID: 27021288.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genome-wide analyses of aggressiveness in attention-deficit hyperactivity disorder. AU - Brevik,Erlend J, AU - van Donkelaar,Marjolein M J, AU - Weber,Heike, AU - Sánchez-Mora,Cristina, AU - Jacob,Christian, AU - Rivero,Olga, AU - Kittel-Schneider,Sarah, AU - Garcia-Martínez,Iris, AU - Aebi,Marcel, AU - van Hulzen,Kimm, AU - Cormand,Bru, AU - Ramos-Quiroga,Josep A, AU - ,, AU - Lesch,Klaus-Peter, AU - Reif,Andreas, AU - Ribasés,Marta, AU - Franke,Barbara, AU - Posserud,Maj-Britt, AU - Johansson,Stefan, AU - Lundervold,Astri J, AU - Haavik,Jan, AU - Zayats,Tetyana, Y1 - 2016/03/29/ PY - 2015/06/23/received PY - 2016/02/09/accepted PY - 2016/3/30/entrez PY - 2016/3/30/pubmed PY - 2017/9/21/medline KW - ADHD KW - GWAS KW - aggression SP - 733 EP - 47 JF - American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics JO - Am. J. Med. Genet. B Neuropsychiatr. Genet. VL - 171 IS - 5 N2 - 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. SN - 1552-485X UR - https://www.unboundmedicine.com/medline/citation/27021288/Genome_wide_analyses_of_aggressiveness_in_attention_deficit_hyperactivity_disorder_ L2 - https://doi.org/10.1002/ajmg.b.32434 DB - PRIME DP - Unbound Medicine ER -