The genetic correlates of extreme impulsive violence are poorly understood, and there have been no studies that have systematically characterized a large group of affected individuals both clinically and genetically. We performed a genome-wide rare copy number variant (CNV) analysis in 281 males from four Czech prisons who met strict clinical criteria for extreme impulsive violence. Inclusion criteria included age ≥ 18 years, an ICD-10 diagnosis of Dissocial Personality Disorder, and the absence of an organic brain disorder. Participants underwent a structured psychiatric assessment to diagnose extreme impulsive violence and then provided a blood sample for genetic analysis. DNA was genotyped and CNVs were identified using Illumina HumanOmni2.5 single-nucleotide polymorphism array platform. Comparing with 10851 external population controls, we identified 828 rare CNVs (frequency ≤ 0.1% among control samples) in 264 participants. The CNVs impacted 754 genes, with 124 genes impacted more than once (2-25 times). Many of these genes are associated with autosomal dominant or X-linked disorders affecting adult behavior, cognition, learning, intelligence, specifically expressed in the brain and relevant to synapses, neurodevelopment, neurodegeneration, obesity and neuropsychiatric phenotypes. Specifically, we identified 31 CNVs of clinical relevance in 31 individuals, 59 likely clinically relevant CNVs in 49 individuals, and 17 recurrent CNVs in 65 individuals. Thus, 123 of 281 (44%) individuals had one to several rare CNVs that were indirectly or directly relevant to impulsive violence. Extreme impulsive violence is genetically heterogeneous and genomic analysis is likely required to identify, further research and specifically treat the causes in affected individuals.

Children's Faculty Hospital Department of Pediatrics and Adolescent Medicine Kosice Slovakia Department of Pediatrics and Adolescent Medicine Faculty of Medicine of Pavel Jozef Šafárik University Kosice Kosice Slovakia

Department of Psychiatry Faculty of Medicine and University Hospital in Pilsen Charles University Prague Czech Republic Department of Psychiatry 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic Institute for Postgraduate Medical Education Prague Czech Republic Psychology Department National Institute of Mental Health Klecany Czech Republic

Prison Service of the Czech Republic Directorate General Department of Psychology Prague Czech Republic

Psychology Department National Institute of Mental Health Klecany Czech Republic

Psychology Department National Institute of Mental Health Klecany Czech Republic Psychology Department University of New York Prague Prague Czech Republic

Research Unit for Rare Diseases Department of Pediatrics and Adolescent Medicine 1st Faculty of Medicine Charles University Prague Czech Republic

Research Unit for Rare Diseases Department of Pediatrics and Adolescent Medicine 1st Faculty of Medicine Charles University Prague Czech Republic Section on Nephrology Wake Forest School of Medicine Medical Center Blvd Winston Salem North Carolina USA

The Centre for Applied Genomics and Program in Genetics and Genome Biology The Hospital for Sick Children Toronto Ontario Canada

The Centre for Applied Genomics and Program in Genetics and Genome Biology The Hospital for Sick Children Toronto Ontario Canada Department of Molecular Genetics and McLaughlin Centre University of Toronto Toronto Ontario Canada

The Centre for Applied Genomics and Program in Genetics and Genome Biology The Hospital for Sick Children Toronto Ontario Canada Institute of Neuroscience Newcastle University Sir James Spence Institute Royal Victoria Infirmary Newcastle upon Tyne UK

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