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Am J Med Genet B Neuropsychiatr Genet. 2016 Jul;171(5):733-47. doi: 10.1002/ajmg.b.32434. Epub 2016 Mar 29.

Genome-wide analyses of aggressiveness in attention-deficit hyperactivity disorder.

Author information

1
Division of Psychiatry, Haukeland University Hospital, Bergen, Norway.
2
K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, Department of Biomedicine, University of Bergen, Bergen, Norway.
3
Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
4
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
5
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Frankfurt, Frankfurt, Germany.
6
Psychiatric Genetics Unit, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
7
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
8
Biomedical Network Research Centre on Mental Health (CIBERSAM), Barcelona, Spain.
9
Department of Psychiatry and Psychotherapy, Klinik Nürtingen, Nürtingen, Germany.
10
Division of Molecular Psychiatry, Center of Mental Health, University of Würzburg, Würzburg, Germany.
11
Department of Forensic Psychiatry, Child and Youth Forensic Service, University Hospital of Psychiatry, Zurich, Switzerland.
12
Department of Child and Adolescent Psychiatry, University of Zurich, Zurich, Switzerland.
13
Facultat de Biologia, Departament de Genètica, Universitat de Barcelona, Catalonia, Spain.
14
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain.
15
Institut de Biomedicina de la Universitat de Barcelona (IBUB), Catalonia, Spain.
16
Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
17
Department of Translational Neuroscience, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, The Netherlands.
18
Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.
19
Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
20
Department of Clinical Science, University of Bergen, Bergen, Norway.

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.

KEYWORDS:

ADHD; GWAS; aggression

PMID:
27021288
PMCID:
PMC5071721
DOI:
10.1002/ajmg.b.32434
[Indexed for MEDLINE]
Free PMC Article

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