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Rare copy number variation in extremely impulsively violent males
Authors:Jan Vevera,Mehdi Zarrei,Hana Hartmannov  ,Ivana Jedli   kov  ,Dita Mu&#x    lkov  ,Anna P&#x  istoupilov  ,Petra Oliveriusov  ,Helena Tre&#x  lov  ,Lenka Noskov  ,Kate&#x  ina Hoda&#x  ov  ,Viktor Str  necký  ,V  clav Ji&#x  i   ka,Marek Preiss,Kate&#x  ina P&#x  í  hodov  ,Jana &#x  aligov  ,John Wei,Marc Woodbury‐Smith,Anthony J. Bleyer,Stephen W. Scherer,Stanislav Kmoch
Affiliation:Jan Vevera,Mehdi Zarrei,Hana Hartmannová,Ivana Jedličková,Dita Mušálková,Anna Přistoupilová,Petra Oliveriusová,Helena Trešlová,Lenka Nosková,Kateřina Hodaňová,Viktor Stránecký,Václav Jiřička,Marek Preiss,Kateřina Příhodová,Jana Šaligová,John Wei,Marc Woodbury‐Smith,Anthony J. Bleyer,Stephen W. Scherer,Stanislav Kmoch
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 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.
Keywords:antisocial personality disorder  copy number variation  dissocial personality disorder  genetics  impulsive violence  rare variants
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