Citation

Vevera J, Zarrei M, Hartmannová H, Jedličková I, Mušálková D, Přistoupilová A, Oliveriusová P, Trešlová H, Nosková L, Hodaňová K, Stránecký V, Jiricka V, Preiss M, Příhodová K, Šaligová J, Wei J, Woodbury-Smith M, Bleyer AJ, Scherer SW, Kmoch S. Genes Brain Behav. 2019; 18(6): e12536.

Affiliation

Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University, Prague, Czech Republic.

Copyright

(Copyright © 2019, John Wiley and Sons)

DOI

10.1111/gbb.12536

PMID

30411505

Abstract

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 4 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 SNP array platform. Comparing with 15,500 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 behaviour, 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 likely 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.

This article is protected by copyright. All rights reserved.

Language: en

Keywords

Antisocial Personality Disorder; Copy number variation; Dissocial Personality Disorder; Genetics; Impulsive violence; Rare variants