Wake Up Call for Insomnia GWAS

Here is another GWAS, this time for insomnia, that I think buries the lead:

Genome-wide meta-analysis of insomnia in over 2.3 million individuals implicates involvement of specific biological pathways through gene-prioritization

Here's an alternate title:

Based on 1.3 million GWAS, the maximum variance explained was 2.6% and based on 2.3 million individuals the maximum variance explained seems to be only 2% !

- (Hat tip to Veera M. Rajagopal, twitter handle: @doctorveera, who might not really appreciate the hat tip)

Obviously, there is a problem here, when, even when finding novel loci by expanding your dataset, you are getting getting worse "variance explained" from your PRS. I think this suggests that they have already reached their peak, which seems to run in the 2 to 3% range for most behavioral traits. I will once again point out that even this number is suspect, since it is not compared to any null trait. They try to rationalize it by suggesting that that the added data (from 23andMe) was less stringently phenotyped, but you can't have it both ways. Expanding datasets does not appear to give us any more real insight. It just bumps up the number of loci meeting significance, which arguably just a collection of false positives.

As the datasets expands beyond just white Europeans, I suspect this will onlly further water down the success of these studies, since they will not be able to rely as much on pop strat to get correlations.

Bipolar Genetics Makes No Progress

Nice critique by Peter Simons of a genetic study for bipolar disorder among Han Chinese with the diagnosis  of Bipolar Disorder (original study here). A couple of excerpts:

The researchers analyzed thousands of Han Chinese people and found that genetics explained just 2.3% of whether they received a diagnosis of bipolar disorder (BD) or not...

However, it is unclear how tiny correlations like this—which affect but a tiny sample of the population studied and explain less than 3% of the risk for a diagnosis—could help researchers understand the supposed “biological etiology” of bipolar disorder. In fact, they rather show that more than 97% of the reason that someone gets a diagnosis is explained by factors other than biology. 

As I like to point out, even the 3% is quite suspect and is arguably noise and should be tested against a null trait to establish that the 3% is not the null.

Genetic Prediction of Schizophrenia via Polygenic Risk Score Has No Clinical Utility

 A new study from Schizophrenia Bulletin tested various risk factors on a group of individuals in a Netherlands. In addition to other risk factors, they used Polygenic Risk Score (PRS) developed from previous studies. This summarizes the results:

We calculated the relative contribution of each (group of) risk factor(s) to the variance in (change in) mental health. In the combined model, familial and environmental factors explained around 17% of the variance in mental health, of which around 5% was explained by age and sex, 30% by social circumstances, 16% by pain, 22% by environmental risk factors, 24% by family history, and 3% by PRS for schizophrenia (PRS-SZ). Results were similar, but attenuated, for the model of mental health change over time. Childhood trauma and gap between actual and desired social status explained most of the variance.

 This is a weak result all around, but particularly bad was the PRS which had a predictive success of 0.5 % (3% of 17%). Thus, just knowing a person's age and sex was almost twice as predictive as the PRS. If the person had a history of pain or other medical complaints, that alone was 4 times more predictive for schizophrenia. This is simply a dismal failure and the continued hope that this will be good enough to be clinically useful is little more than wishful thinking. Realistically, to be clinically useful, it would have to be 25 to 50 times better than this and I am guessing it has come close to peaking.

Genes for Substance Abuse Has Made No Progress, but Unjustified Optimism Continues

Yet another genetic study of substance abuse:

Using polygenic scores for identifying individuals at increased risk of substance use disorders in clinical and population samples

Highlights:

These PRSs explain ~2.5–3.5% of the variance in AUD (across FT12 and COGA) when all PRSs are included in the same model. 

...usefulness for identifying those at increased risk in their current form is modest, at best 

This was from an all white European sample, ftr, with the assumption that pop strat is accounted for. One can assume, as has been the case, that such pop strat will be found and water this down to next to nothing. That said, is the null 0% or is 2 or 3 % about as low as you can get? I'd be happy to see an example in which a PRS does worse than this.

So is the conclusion that perhaps we are barking up the wrong tree? Of course not:

 Improvement in predictive ability will likely be dependent on increasing the size of well-phenotyped discovery samples. 

The shell game continues...

Learning about the elitist opinions of a study's authors through their dubious study

This preprint of an alleged "study, " "GENETIC CONSEQUENCES OF SOCIAL STRATIFICATION IN GREAT BRITAIN", is the kind of filth that has only been suggested in previous studies, but apparently they are feeling puffed up enough to just go full-on eugenic.  I realize that they believe that what they are saying is backed up by genetic evidence, but that's what the phrenologists thought, as well.  Realistically, I can't fully dispute all of the claims, as I am not familiar enough with the geography of England and the socio-economic aspects of their society.  Nonetheless, it's not hard to see what is happening here, if one really wanted to see it, which is that their beliefs about the genetics of superior sorts (i.e.,  people more like them) are causing them to miss the forest through the trees in terms of stratification of a society.  I am quite confident that I can tell you the authors' politics, socioeconomic and geographic backgrounds and opinions about various mental illnesses, without having met any of them.  It is an elitist view of the world, written by elitists, for the pleasure of other elitists.  They should be ashamed.  So, let's go through this, shall we: