Wednesday, February 13, 2013

I am prompted to dust off my little (well, never) used blog by a paper that was just published in Molecular Psychiatry.  I have gotten a bunch of emails about it, mostly from people who seem to think it contradicts my outlook on behavior genetics. Link here, though it is behind a paywall unless your University gets you through it.  I don't have any criticisms of the study itself, really.  It is timely, well-done and interesting.  I just don't think it is revolutionary, or even a harbinger of something revolutionary; it is a new way of demonstrating something we have known for a long time.

The research group put together a large consortium of studies with genome-wide SNP data on samples of children with IQ scores.  They then searched for genome-wide significance for the individual SNPs (and didn't find any, although they are getting closer), conducted a gene- (as opposed to SNP) based analysis that identified one gene with a significant association with IQ, used genome-wide complex trait analysis to show that common SNPs jointly account for a substantial proportion of the variation in IQ, and built a multi-SNP predictor based on the SNPs most strongly related to IQ, which predicted 1.2, 3.5 and .5 percent of the variation in IQ in three replication samples.

What does all this mean?  To understand it, you have to place it in context:  the first of the three assertions in the title, that IQ is heritable, has been perfectly well established by twin and adoption studies for seventy-five years.  It's good to show once again without the twins, but it is hardly news.  The second assertion, that it is highly polygenic, has been pretty obvious for a long time also, and has become moreso recently.

But what of the GCTA and the predictive composite?  GCTA is more like a twin study than it is like gene-finding.  SNP arrays are used to define pairwise genomic similarity among "unrelated" individuals, and then genomic similarity is compared to phenotypic similarity.  So yes, the heritability that was detected via quantitative genetics exists down in the SNPs somewhere, but where else would it have been?  When the researchers create composites of actual SNPs, instead of just identifying SNP-based variance, they can account for a weighted mean of 1.7% of the variance, which is a correlation of r=.13.  That, to me, is the bottom line:  if we were start a program tomorrow to take SNPs from newborns and predict their intelligence, we would do so at a level much worse than predicting from the parent's income, for example, never mind from their IQ.  And this part of the story is not one that we expect to improve as samples get bigger.  The 1.7% was based on all the SNPs, not just those reaching some magical level of significance.

What we do expect as samples get bigger is that maybe some individual SNPs will reach that magical level.  Steve Hsu predicts so, here.  I say so what.  Sure, if samples reach into the hundreds of thousands, a few SNPS with truly tiny effect sizes will be significant.  Once again:  no one sensible thought that maybe SNPs weren't associated with intelligence; the twin studies demonstrate that SNPs have to be associated with intelligence.  The real question is whether, short of growing everyone an identical twin, we can figure out the combinatorial rules by which bits of DNA combine, so we can build useful scientific explanations or prediction models.  I still see no signs that we are headed in that direction.


Timothy Bates said...
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Timothy Bates said...

Nice post, Eric.

Lot's of food for thought. I think the results are more important than you do at present, I think.

Started to explain why here, but it got a bit longer than I expected. So, I made a blog too :-)