Sunday 16 November 2014

Wife-beaters and axe-murderers

My pal P in Boston alerted me to a new study out of Finland which investigated the genetic basis of violent crime. Genetic association studies in humans need to be approached with your crap-detector switched to maximum red alert.  Every few years some 'science' journalist will report that some boffins have discovered the gene 'for' homosexuality which has the dimmer members of the reactionary public sharpening their pitch-forks and looking for a tinder-box for their torches.  As the commentary in the Economist [always good for sensible analysis] says, this all sets off a whoop whoop genetic determinism alert.  This is the touchy concept that you can be damned by your genetic heritage and is triggered when anyone suggests that people who have a Y chromosome or have a really good tan are different from those who lack these attributes.  Even when there is no suggestion that possessors or lackers are better or worse than the other lot, it still gets liberal people exercised. Men can't multitask, women can't read maps are not too edgy, but don't even mention intelligence or athletic ability or crime statistics.

The group led by Jan Tiihonen work out of the Karolinska Institutet in Sweden but their data came from prisoners in Finland. They identified variants in two genes MAOA & CDH13 which were far more common in perps who were in chokey for violent crimes. These genes were at normal frequency in ordinary shop-lifting, car-thieving, handbag-snatching criminals. MAOA codes for a protein Monamine Oxidase A whose task is to breakdown some classes of neurotransmitters after they have delivered their load. If the MAOAs are less efficient because of the mutation then the neurotransmitter will hang around for another round of transmission and particular neurons will continue to fire off. This is not the first time MAOA has been identified in this context.  Another previously named gene is HTR2B which codes for the receptor that recognises the neurotransmitter serotonin, and then implements a firing cycle.  You can imagine that another way in which neurons can continue to fire is because of changes in sensitivity receptor-side rather than excess on the supply-side.

But while the Karolinska team found no statistical signal for HTR2B in their cohort of violent Finns, they identified another player in the game CDH13 which is a cadherin, a class of proteins which stick out of cells and promote adhesion between them.  The Economist claims that CDH13 is involved in axon development but wikipedia makes no mention of this.  Tiihonen identified the variant CDH13 by doing a genome-wide association study - searching through all the genes looking for those that were positively associated with their cohort of beserkers.  There are ethical, philosophical, statistical and mathematical problems with such studies but that hasn't stopped me from using the technique myself.  The main problem is one of multiple testing: with 23,000 protein coding genes, all of which can have some sort of variability between normal you and your fighting mad cousin Lenny, you're bound to find one or two which are associated with whatever you're interested in.  Association does not necessarily identify a cause.

But the more serious civil libertarian issue is the false positives. Before you advocate testing for MAOA status at birth and tattooing the result on each forehead reflect on this. For every low-activity MAOA-possessing axe-murderer in jail, in Finland or in your own country, there are thousands of folks out there on the street who also have a low-activity MAOA but have no intention of beating anyone up. An earlier study in New Zealand, went the extra mile and did a painstaking psychological history for each case as well as the high-tech lab work.  They found that the Kiwi violent offenders, not only carried the MAOA variant but also had experienced an abusive upbringing. As ever, it's in the interaction terms: genes may be important but they don't act in a vacuum - the environment also plays its part.  It's more difficult to think about complex grey-scale situations than to call things black (you) and white (me, of course).

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