Genomic Architecture of Aggression: Rare Copy Number Variants in Intermittent Explosive Disorder

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.