quality:correction
Genetics

In general, differences in a continuous phenotype such as aggression are likely to result from the action of a large number of genes each of small effect, which interact with each other and the environment through development and life.

In a non-mammalian example of genes related to aggression, the fruitless gene in fruit flies is a critical determinant of certain sexually dimorphic behaviors, and its artificial alteration can result in a reversal of stereotypically male and female patterns of aggression in fighting. However, in what was thought to be a relatively clear case, inherent complexities have been reported in deciphering the connections between interacting genes in an environmental context and a social phenotype involving multiple behavioral and sensory interactions with another organism.

In mice, candidate genes for differentiating aggression between the sexes are the Sry (sex determining region Y) gene, located on the Y chromosome and the Sts (steroid sulfatase) gene. The Sts gene encodes the steroid sulfatase enzyme, which is pivotal in the regulation of neurosteroid biosynthesis. It is expressed in both sexes, is correlated with levels of aggression among male mice, and increases dramatically in females after parturition and during lactation, corresponding to the onset of maternal aggression. At least one study has found a possible epigenetic signature (i.e., decreased methylation at a specific CpG site on the promoter region) of the serotonin receptor 5-HT3a that is associated with maternal aggression among human subjects.

Mice with experimentally elevated sensitivity to oxidative stress (through inhibition of copper-zinc superoxide dismutase, SOD1 activity) were tested for aggressive behavior. Males completely deficient in SOD1 were found to be more aggressive than both wild-type males and males that express 50% of this antioxidant enzyme. They were also faster to attack another male. The causal connection between SOD1 deficiency and increased aggression is not yet understood.

In humans, there is good evidence that the basic human neural architecture underpinning the potential for flexible aggressive responses is influenced by genes as well as environment. In terms of variation between individual people, more than 100 twin and adoption studies have been conducted in recent decades examining the genetic basis of aggressive behavior and related constructs such as conduct disorders. According to a meta-analysis published in 2002, approximately 40% of variation between individuals is explained by differences in genes, and 60% by differences in environment (mainly non-shared environmental influences rather than those that would be shared by being raised together). However, such studies have depended on self-report or observation by others including parents, which complicates interpretation of the results.

The few laboratory-based analyses have not found significant amounts of individual variation in aggression explicable by genetic variation in the human population. Furthermore, linkage and association studies that seek to identify specific genes, for example that influence neurotransmitter or hormone levels, have generally resulted in contradictory findings characterized by failed attempts at replication. One possible factor is an allele (variant) of the MAO-A gene which, in interaction with certain life events such as childhood maltreatment (which may show a main effect on its own), can influence development of brain regions such as the amygdala and as a result some types of behavioral response may be more likely. The generally unclear picture has been compared to equally difficult findings obtained in regard to other complex behavioral phenotypes. For example, both 7R and 5R, ADHD -linked VNTR alleles of dopamine receptor D4 gene are directly associated with the incidence of proactive aggression in the men with no history of ADHD.