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Genetic Factors Tied to Violent Behaviors

— Account for up to 10% of extreme violent crime, authors say.

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Variants in two genes were significantly more common in Finnish criminals convicted of multiple violent crimes compared with the general population, researchers said.

Statistical analysis indicated that 5% to 10% of all severe violent crime in Finland could be attributed to these variants, affecting the genes for monoamine oxidase A (MAOA) and CDH13, a neuronal membrane adhesion molecule, according to , of the Karolinska Institute in Stockholm, and colleagues.

Offenders who had committed 10 or more serious violent crimes were significantly more like to carry one of several loss-of-function variants in the MAOA gene (odds ratio 2.66, 95% CI 1.60-4.42) or the so-called rs11649622 variant in the CDH13 gene (OR 2.72, 95% CI 1.77-4.15), versus participants in population-based survey studies in Finland who were considered representative of the general population.

Criminal offenders with no violent crime convictions showed no increases in risk of carrying the flagged MAOA/CDH13, with an OR of 1.12-1.13 relative to the population-based sample, which did not approach statistical significance.

In their report published online in , they acknowledged that crime "is a complex phenomenon, and the outcome is shaped by both genetic and environmental factors."

But that doesn't mean that genetic contributors cannot be identified, they argued. "It is plausible that while research of the genetic background of criminal or violent behavior is hampered by many confounding factors, focusing on extreme phenotypes might yield more robust results," Tiihonen and colleagues wrote.

"This was demonstrated in our analysis on the association between rs11649622 [variant in the CDH13 gene] and MAOA genotypes versus the number of committed violent crimes, showing clear dose-response effects."

, director of forensic psychiatry at Vanderbilt University in Nashville, told 51˶ in an interview that the study was interesting in that it identified genetic contributors to violent behavior with a plausible biological basis.

Nevertheless, said Montgomery, who was not involved with the study, the relatively low population-attributable risk meant that there is no immediate practical application, since many individuals carrying the risk alleles identified in the study have no history of violence, and many violent individuals don't carry them.

In an initial discovery phase, Tiihonen and colleagues relied on genetic information obtained from 215 nonviolent offenders and 622 individuals convicted of violent crimes. In the latter group, 84 had committed 10 or more violent crimes and were considered "extremely violent offenders." Specific crimes included a variety of homicides and attempted homicides. Persons convicted only of sex-related crimes were excluded from the study.

The researchers then sought to replicate the findings in a second offender cohort consisting of 114 murderers who had undergone forensic psychiatric evaluations "because of the extreme nature of their crimes." A different population-based survey sample served as controls.

The finding that certain MAOA/CDH13 variants were more common in the recidivist violent offenders first emerged from a genome-wide analysis that used one population-based survey sample as control. The association with these variants was then confirmed in comparisons using different population-based samples as the controls.

A negative finding of note, Tiihonen and colleagues indicated, was that the genetic associations were specific for violent crime and were not significantly related to substance abuse or to antisocial personality disorders generally. Moreover, they said, "[records of childhood] maltreatment did not modify the risk in any way."

They noted that the link between violent behavior and loss of function in MAOA activity made biobehavioral sense -- the enzyme is involved in dopamine metabolism, and diminished activity has been linked to aggressive behavior in rodents and in humans.

The involvement of CDH13, a mediator of neuronal migration and proliferation, is more of a mystery, the researchers acknowledged. Earlier studies have suggested a role in neural connectivity such that sequence alterations could create a basis for impaired impulse control, Tiihonen and colleagues suggested.

Disclosures

The study was funded by the Finnish Ministry of Health and Social Affairs through the development fund for Niuvanniemi Hospital, Finland.

Some co-authors disclosed receiving funds or grants from Instrumentarium Science Foundation, Orion-Farmos Research Foundation, and the Academy of Finland.

Tiihonen and co-authors disclosed no relevant relationships with industry.

Primary Source

Molecular Psychiatry

Source Reference: Tiihonen J, et al "Genetic background of extreme violent behavior" Mol Psych 2014; DOI: 10.1038/mp.2014.130.