Genomic architecture of aggression: Rare copy number variants in intermittent explosive disorder

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 156B; no. 7; pp. 808 - 816
• Main Authors: Vu, Tiffany H., Coccaro, Emil F., Eichler, Evan E., Girirajan, Santhosh
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.12.2011; Wiley-Liss
• Subjects: 15q13.3; Adult and adolescent clinical studies; Aggression; Aggressive behavior; array CGH; Autism; Biological and medical sciences; Chromosome 1; Chromosome deletion; copy number; Disruptive, Impulse Control, and Conduct Disorders - diagnosis; Disruptive, Impulse Control, and Conduct Disorders - genetics; DNA Copy Number Variations - genetics; Explosives; Female; Genome, Human - genetics; genomic disorders; genomics; Humans; Male; Medical genetics; Medical sciences; Mental disorders; Movement disorders; Neurodegenerative diseases; Parkinson's disease; Pedigree; Personality; Personality Disorders - diagnosis; Personality Disorders - genetics; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Schizophrenia; segmental duplication; Social behavior disorders. Criminal behavior. Delinquency; Chromosomal aberration; Impulse control disorder; array CGH; genomic disorders; Copy number; 15q13.3; aggression; Variant; segmental duplication; Segmental; Abnormal chromosome; Intermittent explosive disorder; Chromosome duplication
• ISSN: 1552-4841; 1552-485X; 1552-485X
• DOI: 10.1002/ajmg.b.31225

Copy number variants (CNVs) are known to be associated with complex neuropsychiatric disorders (e.g., schizophrenia and autism) but have not been explored in the isolated features of aggressive behaviors such as intermittent explosive disorder (IED). IED is characterized by recurrent episodes of aggression in which individuals act impulsively and grossly out of proportion from the involved stressors. Previous studies have identified genetic variants in the serotonergic pathway that play a role in susceptibility to this behavior, but additional contributors have not been identified. Therefore, to further delineate possible genetic influences, we investigated CNVs in individuals diagnosed with IED and/or personality disorder (PD). We carried out array comparative genomic hybridization on 113 samples of individuals with isolated features of IED (n = 90) or PD (n = 23). We detected a recurrent 1.35‐Mbp deletion on chromosome 1q21.1 in one IED subject and a novel ∼350‐kbp deletion on chromosome 16q22.3q23.1 in another IED subject. While five recent reports have suggested the involvement of an ∼1.6‐Mbp 15q13.3 deletion in individuals with behavioral problems, particularly aggression, we report an absence of such events in our study of individuals specifically selected for aggression. We did, however, detect a smaller ∼430‐kbp 15q13.3 duplication containing CHRNA7 in one individual with PD. While these results suggest a possible role for rare CNVs in identifying genes underlying IED or PD, further studies on a large number of well‐characterized individuals are necessary. © 2011 Wiley‐Liss, Inc.