ONE of the scientific subjects best guaranteed to get people hot under the collar is genetic determinism, especially if what is allegedly being determined is behavioural. Studies of adopted children (and particularly of twins adopted at birth by different sets of parents) suggest some behavioural traits are indeed heritable. Geneticists, though, have had difficulty identifying specific genes whose variants, known as alleles, cause different predispositions in those possessing different versions. That is why a new piece of research on one of the few genes for which such evidence exists is likely to get considerable scrutiny and cause much controversy—not least because the work in question suggests that a second gene, hitherto fingered as a cause of behavioural variability, has no effect, while a third, hitherto unfingered, does.

The first two genes are called MAOA and HTR2B. The behaviour they allegedly predispose people to is aggression. The latest data, collected by Jari Tiihonen of the Karolinska Institute, in Stockholm, and his colleagues, and published in Molecular Psychiatry, come from convicted criminals in Finland, some of whom were banged up for violent crimes and some for offences such as theft that involved no violence.

Breaking the code

MAOA encodes monoamine oxidase A, an enzyme that degrades molecules called monoamines. This group includes some of the best-known neurotransmitters, substances that carry signals between nerve cells. Among them are serotonin and dopamine, both of which affect mood and behaviour. HTR2B encodes one of the receptor molecules for serotonin.

Dr Tiihonen picked MAOA for investigation because two previous studies had suggested some of its alleles (specifically those with low activity, which thus increase levels of the neurotransmitters in question), might have a role in promoting violence. The first of these investigations involved a Dutch family, many of whose members had low-activity MAOA. The second, conducted in New Zealand, suggested that a combination of low-activity MAOA and an abusive upbringing promotes a violent temper, though low-activity alleles by themselves do not. HTR2B had previously been flagged up as a risk factor for violence in only one human study, but experiments on mice confirmed the idea was plausible.

Dr Tiihonen and his colleagues divided their convict volunteers into those who had never committed a crime of violence (defined as homicide, attempted homicide and battery—though sexually motivated assault was excluded, to avoid confusing the data) and those who had. They then subdivided the second category into the moderately violent (who had committed fewer than ten such crimes) and the extremely violent (who had committed ten or more).

Non-violent prisoners, the researchers discovered, were not more likely than the average Finn to have a low-activity MAOA gene. Violent ones, however, were. And extremely violent ones were a lot more likely to. This result does indeed suggest that low-activity alleles of MAOA can have an effect on the development of violent tendencies. By contrast, the suspect version of HTR2B was as common in non-violent as in violent prisoners, and also as in the population at large.

Dr Tiihonen’s examination of these two genes was a proper, hypothesis-driven investigation. The idea that a third, CDH13, might be involved, though, was the result of a genetic fishing expedition, or genome-wide association study as they are known in the trade. This looked for stretches of DNA more common in violent prisoners than non-violent ones, and then identified what they were.

Such studies should be treated with caution because, since the whole genome is being examined, spurious correlations are inevitable. However, the team did check their conclusion against another set of prisoners before publishing it, and found the same result. Moreover, cadherin 13, the protein encoded by CDH13, also affects nerves. It helps regulate the growth of axons—the filamentous and often extremely long protuberances of nerve cells that reach out to convey a nerve’s message to the place where it is needed, so this gene’s candidacy as a violence enhancer is at least plausible.

The net effect of Dr Tiihonen’s work, then, is to confirm the idea that one particular gene’s alleles can affect violent behaviour, while eliminating a second candidate and introducing a third. But the crucial question is, what is meant by the word “affect”? Something like half the population has a low-activity MAOA allele, and, obviously, the overwhelming majority of them are not violent criminals.

Dr Tiihonen and his colleagues estimate, on the basis of their study, that pertinent alleles of MAOA and CDH13 together play a part in 5-10% of Finland’s violent crime, so even their own research suggests these genotypes are minority causes of such offences. Part of the explanation for the former’s role may lie in the New Zealand study, which showed the importance of interactions between someone’s upbringing and his genes. Also, as Dr Tiihonen observes, in Finland, most violent crime takes place under the influence of alcohol or amphetamines, both of which boost dopamine levels. There is evidence that high dopamine levels are linked to violent behaviour, so perhaps the double whammy which is created by adding the drug-boost effect to that of the enzyme tips some people over the edge.

That is speculation. But what Dr Tiihonen and his team have done is provide a third data point for the hypothesis that low-activity MAOA can, in the right circumstances, trigger violence. This does not prove the hypothesis. But it should make people take it more seriously.