January 4, 2013

Mistargeted genetic sequencing

According to the New York Times, researchers at the University of Connecticut are planning to sequence the genome of the Newtown school murderer.  They aren’t specifically saying why, though the obvious interpretation is that they are looking for genetic causes of violence (there could be more cynical interpretations, but let’s not go there).  This seems a bad idea.

Firstly, they won’t find anything.  If you have a difference between groups of people that is completely explained by a single genetic variant, you can find the variant with genotypes on only a few dozen people in each group (eg blond hair in Melanesians, intolerance of the HIV drug abacavir).  That’s still a lot more than the number of mass murderers they will have conveniently available any time soon.   If the phenomenon you’re trying to explain is not controlled by a single genetic variant, the necessary sample sizes shoot up by orders of magnitude.  The problem is that an individual has perhaps 2-3 million differences from the reference genome, tens of thousands of which will never have been seen before. These variants are spread through 20 000 genes, regulatory regions, poorly-understood bits of non-coding RNA, and genuine junk DNA.  There would be no way to tell which of these differences is the ‘real cause’ even if there were a ‘real cause’ to find.

Secondly, what would they do with it if they found it? We already know of a common single-gene genetic variant that, in US residents, increases the risk of becoming a mass gun murderer by a factor of about 60. People with this variant are actually more likely to be employed as armed guards, and are specifically targeted by gun industry advertising.  A genetic effect would have to be much larger than this to be actually useful, and that’s before you start to consider the ethical and legal implications of screening for propensity to possibly commit a crime in the future.

And finally, if you want to understand biological contributions to violence for public health reasons, it probably makes more sense to focus on the 99+% of murders that aren’t mass shootings.

(a similar list from Jeff Leek at Simply Statistics)

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Thomas Lumley (@tslumley) is Professor of Biostatistics at the University of Auckland. His research interests include semiparametric models, survey sampling, statistical computing, foundations of statistics, and whatever methodological problems his medical collaborators come up with. He also blogs at Biased and Inefficient See all posts by Thomas Lumley »