If You Can't Make it Happen for Schizophrenia

 This is an expansion of a previous Schizophrenia GWAS:

Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

This is the PGC schizophrenia study. We hadn't really had an update since 2014. It appears they buried the lead with the usual false optimism. They went from 36,000 cases in the previous study to 69,000 in this one. We have been promised that polygenic risk scores (PRS) would explain more and more of the "missing heritablity" as the study sizes increased. Well, in this case, the PRS variance explained went from 3.4% to ... 2.6%. Of course, that 3.4% was apparently an error anyway.They also admit that their previous calculation of 3.4%, often cited in other papers, was calculated in error and was probably lower. Is that to make it look like the 2.6% is not that bad?

The fact of the matter is that this is a very bad result. This is not even a within family calculation, which one might expect to be very close to 0%. I think at this point, getting 2 or 3 percent of the variance explained is essentially a null finding, and I challenge any authors who claim otherwise to compare it to obvious null traits.

I might have more to say about this related to the loci they say reached significance, but can't find the old PGC data to compare it with directly. In any case, the only thing that increasing N does is bolster the number of "significant" loci and I expect none of these loci will independently meet statistical significance in any other study.

What this study really suggests, when you take away the spin, is that the entire model of a polygenic mechanism for schizophrenia is pie in the sky. This points to a larger problem, which is that if any psychiatric trait should be due to a physical (genetic) cause, one would think schizophrenia would be a sure thing. If you can't make it happen for schizophrenia, good luck making it happen for dubious diagnoses like ADHD or really any other psychiatric trait.

Phrenology is Alive and Well in 2020

 When the Human Genome Project began in 1990, there were visions of identifying genes for psychiatric disorders, personality traits, intelligence, character, etc. The dawning of a new age. So let's check in and see how that's going 30 years later in this exciting new study:

Genome-wide meta-analysis of brain volume identifies genomic loci and genes shared with intelligence

This, friends, sounds a bit like phrenology.  

If you are not familiar with phrenology, it was the study of the various protrusions of the skull to determine a person's intelligence, character, personality and, well, whatever you wanted to read into these lumps and bumps, measured by a pair of calipers. It was discredited a long time ago and has some very racist undertones that were driving it as well. Anyone interested in this subject might start with Stephen Jay Gould's, "The Mismeasure of Man." 

The idea behind measuring bumps on the skull is that they told you something about the size or shape of the brain underneath. This premise, in and of itself, that bigger brain regions make a person "more" of something, whether that's intelligence, violence or madness, is absurd enough, but the idea that you could measure it via skull protrusions adds another layer of absurdity.

Well, this study tries to get around that, at least partially, by using a better set of calipers. In this case, MRI (magnetic resonance imaging).

Genetic homogeneity does not reduce individuality (in fish)

 This Study takes genetically identical fish and puts them in indentical environments and demonstrates that they show a lot of individuality:

we find that (i) substantial individual variation in behaviour emerges among genetically identical individuals isolated directly after birth into highly standardized environments and (ii) increasing levels of social experience during ontogeny do not affect levels of individual behavioural variation. In contrast to the current research paradigm, which focuses on genes and/or environmental drivers, our findings suggest that individuality might be an inevitable and potentially unpredictable outcome of development.

 This, of course, is a fish study, but if even fish have such individuality, I think it is a good bet that the same can be said for humans.