Monday, January 31, 2011

Hussman Weekly Market Comment: Mapping the Molecular Pathway of Autism

Last week, in collaboration with the Hussman Institute of Human Genomics at the University of Miami, we reported a new molecular pathway for autism. The study, entitled "A Noise-Reduction GWAS Analysis Implicates Altered Regulation of Neurite Outgrowth and Guidance in Autism ", was published in the open-access, peer-reviewed journal Molecular Autism (the paper is immediately available as a PDF, with diagrams and tables following the references. The formatted publication version should be online within a week or two).

The UM School of Medicine published a nice piece about it: Economist Revolutionizes Mapping of Genetic Pathway for Autism.

Why would an economist be doing genetics research?

At this point, some background is probably a good thing. Just over two years after my son JP was born, he was diagnosed with autism. That's shorthand, of course, because as any autism parent knows, the period between feeling that something is wrong and the time we accept a diagnosis involves such an endless parade of doctors, therapists and other professionals that it might as well include floats, Disney characters and a marching band. As the son of two physicians, having "jumped the track" from medicine in college, I decided that there was something inherently wrong with a world where parents were essentially told "Sorry, but your child has autism. We don't know what causes it, so we have very little advice to offer, except for early intervention - good luck with the cost of that - and a few medications. There are some charlatans and snake-oil salesmen down the street you might look into. And thanks for stopping by."

I spent four years at Stanford for my doctorate in Economics. JP is nearly 17. If you're passionate about something, you can learn a lot in that amount of time. By 2001, I had written a piece for the Journal of Autism and Developmental Disorders (Suppressed GABAergic inhibition as a common factor in suspected etiologies of autism). GABA is the main inhibitory neurotransmitter in the brain, and reduces the tendency of neurons to "fire" too easily. The basic idea of the GABA paper was to connect multiple lines of research which, taken together, suggested that autism might involve an imbalance between excitatory and inhibitory activity in the brain. A couple of years later, a genetics team led by Dr. Margaret Pericak-Vance (now at the University of Miami) identified an association between autism and a number of GABA receptor subunits. Perhaps because Dr. Pericak-Vance (Peggy) is a parent with her own special mission - visit - we instantly became friends, and have collaborated ever since.

I spend almost all of my time in one of three activities - finance, family or charitable projects through the Hussman Foundation. In recent years, much of the foundation's research has been centered on autism. Meanwhile, the finance research has been centered on "ensemble methods" to integrate the information from multiple data sets, and to better measure both risk and uncertainty*. As it happens, statistical methods can be adapted to approach difficult problems in both genetics and finance. So as we developed various approaches to integrate multiple data sets in our finance research, it was natural to extend those methods to deal with genetics data.

* In case separating "risk" from "uncertainty" seems like a distinction without a difference, risk is the extent to which possible outcomes are spread around a known average outcome, given that you know which "state of the world" you're in. Uncertainty is the extent to which the "state of the world" is itself in doubt, so even the average outcome is in question. For example, risk measures the chance that you'll roll something other than 7 given that you know that two six-sided dice are being thrown. Uncertainty is the possibility that the dice themselves might instead have eight, twelve, or twenty sides without your knowledge. Similarly, risk is the probability that the market will decline, given that you know that the economy is in a typical post-war economic cycle. Uncertainty is the possibility that the true economic environment might correspond more closely to the Great Depression than to the post-war period. The difference isn't trivial.


Related links:

"A Noise-Reduction GWAS Analysis Implicates Altered Regulation of Neurite Outgrowth and Guidance in Autism"

Economist Revolutionizes Mapping of Genetic Pathway for Autism