Genetic architecture for human aggression: A study of gene–phenotype relationship in OMIM

Abstract

Genetic studies of human aggression have mainly focused on known candidate genes and pathways regulating serotonin and dopamine signaling and hormonal functions. These studies have taught us much about the genetics of human aggression, but no genetic locus has yet achieved genome‐significance. We here present a review based on a paradoxical hypothesis that studies of rare, functional genetic variations can lead to a better understanding of the molecular mechanisms underlying complex multifactorial disorders such as aggression. We examined all aggression phenotypes catalogued in Online Mendelian Inheritance in Man (OMIM), an Online Catalog of Human Genes and Genetic Disorders. We identified 95 human disorders that have documented aggressive symptoms in at least one individual with a well‐defined genetic variant. Altogether, we retrieved 86 causal genes. Although most of these genes had not been implicated in human aggression by previous studies, the most significantly enriched canonical pathways had been previously implicated in aggression (e.g., serotonin and dopamine signaling). Our findings provide strong evidence to support the causal role of these pathways in the pathogenesis of aggression. In addition, the novel genes and pathways we identified suggest additional mechanisms underlying the origins of human aggression. Genome‐wide association studies with very large samples will be needed to determine if common variants in these genes are risk factors for aggression. © 2015 Wiley Periodicals, Inc.

Genetic Association Study of Childhood Aggression across raters, instruments and age

“…Children typically display AGG early in life, after which symptoms tend to diminish [6, 7], although in some individuals AGG persists into adulthood [8]. AGG is also part of numerous childhood and adult disorders [9], including oppositional defiant disorder (ODD) and conduct disorder (CD)[10]. In its extreme forms, AGG may be considered a disorder by itself – inflicting a huge personal and financial burden on the individual, their relatives, friends, and society as a whole [11].…”

Reciprocal moderation by Toxoplasma gondii seropositivity and blood phenylalanine – tyrosine ratio of their associations with trait aggression

“…Genetic polymorphisms involved in altered dopamine receptor and transporter activities as well as enzymes involved in the metabolism of dopamine have been identified in association with aggression in humans and animals [65, 66]. The direction of the relationship between dopamine and aggression is far from unequivocal.…”

Comparative mRNA analysis of behavioral and genetic mouse models of aggression

“…Consequently, current research aims to identify genetic variants associated with aggressive behaviors, which may help to inform candidate gene selection and the identification of gene pathways to gain further understanding of the genetic substrate of this complex trait [Kudryavtseva et al, 2015;Waltes et al, 2015;Zhang-James and Faraone, 2015]. Gene selection has predominantly been driven by inspecting genes and neurobiological pathways with an established association with aggression, including the serotonin (5-HT) gene, levels of which were found to be low in more aggressive individuals.…”