PTSD and the GWAS Hype Machine

A new PTSD GWAS makes a few bold claims.  I think it's a good example of the kind of hype that these studies, which show next to nothing, crank out to hype their results. In this puff piece related to the study, they start with:

Large study reveals PTSD has strong genetic component like other psychiatric disorders

Which 1. It does not and 2. Is not really shown to be true of other psychiatric disorders, either, except in the same hyped fashion as this study. Now let's look at this from the same puff piece:

The study team also reports that, like other psychiatric disorders and many other human traits, PTSD is highly polygenic, meaning it is associated with thousands of genetic variants throughout the genome, each making a small contribution to the disorder. Six genomic regions called loci harbor variants that were strongly associated with disease risk, providing some clues about the biological pathways involved in PTSD.

 If it is highly polygenic, on what basis are they saying this if only 6 loci were strongly associated with disease risk (this is not even accurate, as I'll discuss in moment)? "Genome-wide, a substantial number of variants had some level of association with PTSD, showing the disorder to be highly polygenic," What this is saying is that there are other loci (presumed genetic variants) that did not reach significance, but they include through the subterfuge of "polygenic scores." There is no basis, other than the hopefulness of those doing these studies, that these below significant findings are anything more than non-significant findings. I'll  also note that none of these 6 loci were found in previous studies. Thus, this is an entirely unreplicated study. Now, let's take a look at the loci they did claim to find:

Depression and Bipolar: Looking at the Positive While Inadvertantly Demonstrating the Negative

I wanted to critique this study which I admittedly struggled to get my head around, so I needed to get help from one of the authors on Twitter. In short, it takes data from two previous studies of depression and bipolar disorder and recombines them. Here is his given explanation:

The combination of the MDD and the bipolar data (which have not been combined in this way before). That is, we are seeing some loci have statistical evidence for "MDD or bipolar" versus control individuals that we haven't seen when looking at either individually so far.

I'm not really sure if that is what they established even on its face since, as I understand it, they simply combine the data from the two studies and perform new GWAS's for both Bipolar Disorder and Depression, creating a new case vs. control for both (I welcome the authors giving a better explanation than I'm putting forth, lest I be accused of creating a straw man. I really just don't fully understand the underlying premise). In doing so, they came up with 15 new loci related to these disorders without using any new data. I believe the point here is to show that bipolar disorder and depression have some genetic commonalities that were demonstrated. They go on to assess these further, but I suggest maybe the lede was buried here and that the study demonstrated another, perhaps more plausible, conclusion: That the original significant loci were false positives, as are these. Let me explain below the fold:

Here Come the Gay Genes

This is a new GWAS related to homosexuality or "same-sex, sexual behavior" as they describe it. Before I even begin this critique, I'll point out the obvious-to-ask question from any such claim, as noted in the study:

We observed in the UK Biobank that individuals who reported same-sex sexual behavior had on average fewer offspring than those of individuals who engaged exclusively in heterosexual behavior... This reproductive deficit raises questions about the evolutionary maintenance of the trait, but we do not address these here.

Yes, it certainly does raise that question. I understand that a thousand explanations have been thrown out for this, none of which has any evidence to back it, and suggest the possibility that we are working with an absurd premise.
Now let's go back to the description of "same-sex, sexual behavior." By what  criteria do we group some kid who, say, had one same-sex sexual experience at summer camp with someone who identifies as homosexual. You would group such and individual as "non-heterosexual"? That seems a stretch and ignores their self-identification. Is there some causal relationship between these two things, genetic or not? I don't think anyone could realistically group these individuals together for a study of this nature. I question even doing a study of this nature, but I think that one would want to first identify individuals that are clearly homosexual rather than confound the study with what might largely be a culturally related experimentation phase.
Once again, I might add, the UK BioBank has been noted in a few recent studies to be replete with population stratification issues, notably related to age and it is noted that young people who participate have higher rates of a same-sex experience. I won't get into too much detail along these lines other than to suggest that such population stratification could easily account for the few significant loci that were found. Now, let's look at some of the numbers and the dubious claims of replication behind the fold:

PTSD GWAS: Another fast and loose with the term "Replication"

This study, a GWAS for PTSD (or symptoms related to PTSD, might be more accurate), like most found a few loci with significant p values. They found 8 in a sample of 120,000 "European Americans" and zero in a sample of 20,000 African Americans. I'd say this is what you might expect for the false positive rates of such studies. They go on to claim that it was "replicated in the UK Biobank." I'll make a quick point after the fold:

Another Unreplicated, hyped study of Anorexia Nervosa

This post takes a quick look at this GWAS study for Anorexia Nervosa. Let me start this off by saying that Anorexia Nervosa is quite clearly a disorder created by our society and compounded by particular childhood trauma issues that I won't get into here. Moreover, looking at this disorder as some kind of metabolic disease and trying to pass it off as a genetically based disorder is very unfortunate and I think shows some real lack of understanding of clinical disorders, and bizarrely reduces it to chemical mechanisms.  In the long list of authors for this paper, I would hope at least a few have some actual clinical experience with this disorder, but you wouldn't get a sense of it from the paper.
Now that I got that out of the way, let me briefly discuss the paper itself, which follows the usual formula for GWAS these days:

Question:
Does a dog or a bumblebee have a higher IQ?

Another study questions polygenic scores

This new study:

Variable prediction accuracy of polygenic scores within an ancestry group

is yet another in the long line of studies showing that polygenic scores are replete with problems like population stratification and assortative mating. It buries the lede a bit, in that it takes another swing at the so-called "educational attainment" genetics, probably because I sense the authors don't want to completely give up the ship, but let me make a few points about the study.

The Depression Gene that Wouldn't die

This is a good piece about a gene variant that was presumed for a couple of decades to be related to depression, with hundreds of studies surrounding it, leading to more and more theories of how it effects depression. The gene was 5-HTTLPR which is presumably related to serotonin and gave everyone the feels, because it validated the use of Prozac and similar serotonin based drugs. Then it turned out to be bogus. I believe I was asked specifically about this gene in my psychiatry board exam. Another take home message from this is that if you are jumping on some new study purporting to find a gene or genetic variants for a mental disorder, put it in a drawer for a few years and see if it holds up. They never do, but they are never wrong.

Hoping for a House of Cards

I've already done a review of Robert Plomin's "Blueprint," but I take it a step further in this piece in Logos, pondering whether this is really all they've got and, if so, where that leaves the field of psychiatry,  were the whole GWAS/Polygenic Score research behemoth, which has hogged so much of the mental and material resources for furthering the field, finally hits its dead end? You might call it a fantasy piece.

Is This a Successful Study for Bipolar Genetics? That's how they are billing it.

A "new" GWAS came out for Bipolar Disorder. As yet, I have only seen the abstract, but I wonder whether I need to see more? Let me comment on a few things:

"Eight of the 19 variants that were genome-wide significant (P < 5 × 10−8) in the discovery GWAS were not genome-wide significant in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity."

Is that really what it's consistent with? If you have variants that were found to be significant in previous studies and you include the data from those studies in your current study, even if the effect size was small (and, the power now increased), you should expect most of them to retain significance, even if they weren't significant in the new data set independently. The fact that half of them have lost significance is a good indication that most or all of them were false positives to begin with. Moreover, once again, why not do an independent GWAS (I'm assuming they did not) of the new data and compare it to the old data?
Now let's look at the very next sentence:

More pop/strat discussion related to polygenic scores

This article in Quanta magazine highlights a couple of recent studies in which population stratification issues are giving artificially inflated polygenic score results that don't subsequently have validity when looking at even a relatively similar population, much less diverse populations.  These were for height, which seems like the most obvious candidate for a genetic trait for which one could get a valid polygenic score, but they had to walk back previous claims.  If they can't get if for height, one should immediately ask why anyone would take such a score seriously for say, depression, or "educational attainment." They are putting a lot of time and effort into these studies and the best they can say to date is that maybe some of the correlations are valid, but pop/strat has not been ruled out as the exclusive cause of all their SNP correlations and subsequent polygenic scores.

Alzheimer's "Genes". Another Faux Replication

I will make the same point for this GWAS for Alzheimer's Disease. Again, we have an example of meta-analysis, with new data that has never been studied independently folded into previous studies with a claim of more loci "discovered" and, as one person noted, "the gold standard in field," for replication.  It's amazing how they have watered down replication and now try to call this a gold standard.

Genetics and the Need for Certainty: Looking at the World Through a Genetic Lens

Wrote this piece for "Ordinary Times" related to my quixotic battles with genetic studies and the overgeneticization of our society (at least that's where it took me).  I was writing for a presumed non-scientist audience, so maybe it will be a little more understandable and less dry for someone who is interested in the basic debate I'm trying to put out there.  Or not...

The UK BioBank: The Beast of Pop/Strat

Here is yet another study looking at population stratification issues related to GWAS studies and polygenic score results: Apparent latent structure within the UK Biobank sample has implications for epidemiological analysis.
They looked at geographic structure and found that the UK Biobank is subject to a lot of stratification in that regard. They looked at BMI (body mass index), household income, and educational attainment and found all of them to be subject to geographic population stratification, even with principle component analysis.  First they looked at a smaller subset of genetic data from a previous study (ALSPAC)

...we anticipate that the educational attainment of people who migrate for economic reasons differs from people who do not. Educational attainment is therefore aligned to subtle genetic differences even in this apparently geographically and ethnically homogenous population and this is co-incident with axes of ancestry.

They move on to the beast, the UK Biobank:

Britain's Private Schools Makes a Point About Population Stratification

This article about the British private school system is not directly related to genetics, but goes to a point I've made earlier about genetic studies of "Educational Attainment" and how they will inevitably be filled with false positives related to population stratification.  Let me start with a quote from the article:

What particularly defines British private education is its extreme social exclusivity. Only about 6% of the UK’s school population attend such schools, and the families accessing private education are highly concentrated among the affluent. 

So we have a closed off group that has better access to higher educational opportunities, and of course there is a big payoff for them as we can see here:

Copy of my Review of Robert Plomin's "Blueprint"

 I'm told that my review of Robert Plomin's "Blueprint" in Free Associations is sometimes difficult to download on tablets and phone, so I will add a copy of it here:

Biogenetic Overreach by Steve Pittelli 

Blueprint: How DNA Makes Us What We Are (MIT Press, 2018) is the latest book by genetics researcher and author, Robert Plomin. It begins with discussions about twin and adoption studies, an area where Dr. Plomin has extensive experience as a researcher. This serves as a springboard for Plomin to discuss DNA research, particularly “polygenic scores,” for which he possesses an almost evangelical zeal. Mixing this with his own research anecdotes and theories about a self-described “DNA Revolution,” Plomin’s meandering narrative is, at times, difficult to follow and has a utopian feel. 

As Plomin acknowledges, much of the early DNA research related to psychological traits (and most traits in general) failed to find specific genes related to the trait in question. When such genes were found, the experiments were never replicated, creating a “replication crisis” in the field. In Dr. Plomin’s view, this crisis was solved by the larger datasets now available and the polygenic score, which “predicts” the likelihood of particular traits by tallying up the number of genetic variants a person has that have been shown to correspond in some way to particular traits. I would suggest that this is a significant lowering of the bar for replication and does not eliminate the crisis. 

Genes for Ice Cream Flavor preference...

Yes, the bar gets lowered once again as it approaches a Coke vs. Pepsi gene.  This time we have a "study" that purports to find genes for a preference for chocolate vs. vanilla ice cream (and strawberry, of course).  I know, you are thinking I'm making this up, so here it is.  I'm pretty sure, back in the day, I considered using exactly this possibility to mock these studies, but opted on "finding raisins to be tasty."  I'll get a little bit into the study, but first, let me ask anyone reading this to try to catch yourself in that moment between when something absurd was stated and when you convince yourself that it is somehow valid because, you know, it's science and all.  I like to call that the "Emperor has no clothes!" moment.  Maybe that moment has already passed you by, so try, really try, to remember how you felt in those few seconds before you had to tuck it away.  That moment is important.  It's the brief time when one can see, no matter how much they've been inundated with "scientific" pronouncements to the contrary, that this entire field of study might just have a kind of absurdity to it.
Can't go there?  Well, then you have to believe that there are genetic variants for preferring chocolate or strawberry ice cream over vanilla.  Lot's of them, in fact.  Or you have to explain why this study is not valid and other GWAS studies are.  Let's go through this important study:

IQ and longevity claim takes a hit

This paper  calls the lie on this paper:

Arden et al.  The association between intelligence and lifespan is mostly genetic Int J Epidemiology

The claim was not only that IQ was associated with a longer lifespan, but that "genes for IQ" (a fantasy of the IQ people) were directly correlated with longevity.  Great read.  It's all starting to collapse.

Blueprint?

My review of Robert Plomin's, "Blueprint:  How DNA Makes Us What We Are".
(If you are on a tablet or phone, it's easier to read the PDF format)

Yet More Evidence that PRS is Largely a Measure of Population Stratification

Here is another study pointing to the lack of validity of polygenic risk scores.  This one was for height:

We find that the signals of selection using UKB effect-size estimates for height are strongly attenuated or absent. We also provide evidence that previous analyses were confounded by population stratification Therefore, the conclusion of strong polygenic adaptation now lacks support. 

If you aren't able to control for population stratification for something as straight-forward and quantifiable as height, then certainly you won't be able to do better with "Educational Attainment" or really any more complex psychiatric trait or mental construct.  The null here, is that polygenic scores largely measure population stratification and I would be interested in what could be demonstrated that would lead one to reject the null.  Moreover, the failure of PRS also brings into question the polygenic (and, presumably omnigenic) models for phenotypes. 

Stratification and PRS Difficulties

It is becoming clear that population stratification is  a big issue in when assessing polygenic scores.  This study demonstrates:

 Our results emphasize that we have limited understanding of the interplay between our current PS and genetic population structure even within one of the most thoroughly studied populations in human genetics. Therefore, we recommend refraining from using the current PS to argue for significant polygenic basis for geographic phenotype differences until we understand better the source and extent of the geographic bias in the current PS.

Much of the work on this study involved height, so drawing conclusions about more complex mental traits would be even more confounding.  (Would be useful to have a better understanding of the differences in population between Eastern and Western Finland). 

McCRISPR and the Collective Sanctimony of the Scientists Who Made it Happen

I don't want to add too much to the obvious ethical lapse of the recent CRISPR human guinea pig experiment by Chinese genetic scientist, He Jiankui, as there is an endless stream of outraged scientists, exemplified by this article in Nature: CRISPR-baby scientist fails to satisfy critics. I would, however, like to make a point about the collective scientific outrage, exemplified by a few quotes in the article linked above:

“I’m happy he came, but I was really horrified and stunned when he described the process he used,” says Jennifer Doudna, a biochemist at the University of California, Berkeley, and a pioneer of the CRISPR–Cas-9 gene-editing technique that He used. “It was so inappropriate on so many levels.”

So, it was "the process he used" rather than what he did.  If only he had used a more appropriate process.  Let's look at another quote:

Longevity "genetics" appears to be strongly inflated due to assortative mating

This study just came out which used the Ancestry database to assess the genetic heritability of longevity, which has been previously formulated as upwards of 15 to 30%.  They found that, in fact, taking away assortative mating it is below 10%.  They used pedigrees and compared the in-law siblings.
A GWAS in such a scenario, then, would pick up a lot of extraneous, noncausal genetic associations that were really just related to commonalities from assortative mating, leading one to believe that these genes had some specific role for longevity and possibly wasting a researcher's time.
I would be interested in seeing a similar study on educational attainment, as I think it might very well show the same thing.  I have, in fact, postulated just this in previous posts on here.

A Recent Critique of PRS

This preprint (updated) does some mathematical modeling and shows that PRS, even with h2 = 1, is not as useful as previously thought.  I'll spare you the math (which I'm still trying to wrap my head around) and leave you with their conclusion:

"In summary, our investigation clears up some misconceptions on PRS and demonstrates that PRS is not as useful as its name suggests, and as powerful as the genetics community expects neither for predicting polygenic traits. We hope this research will serve as a wake up call to the genetics community in appreciating more about the challenges in studying complex polygenic traits. As such, more resources and efforts can be devoted in performing better experiments and developing better statistical methods." 

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:

"Minimal Phenotyping" to crank up your GWAS hits creates more problems

This study points out that minimal phenotyping (dumping anyone into your GWAS with a 1 or 2 question screening rather than meeting full diagnostic criteria) for major depression is getting hits that are then tied to CNS enrichment (genes found more commonly in the central nervous system, implying some brain mechanism), but the ones that were "enriched" were actually the extra ones picked up by minimal phenotyping.  This is a problem, because CNS enrichment would be expected to be more prominent for those who met the full criteria for MDD, rather than just answering a couple of questions about depression.  This implies that there are likely false positives, or at the very least, non-specific positives, unrelated to major depression.  Thus, when you try to isolate functional neurological aspects of the disorder, either to understand cause or pursue pharmaceutical options, etc., you are likely barking up the wrong tree.  CNS enrichment is also used as a backdoor method to imply the validity of the genetic variants found in particular GWAS studies related to mental disorders.
So, adding to the fact that there have been no independently replicated, significant genetic variants found for depression, to date, even with minimal phenotyping, we also cannot confirm that these genes have any relation to depression by assessing CNS enrichment.

New Depression Study Finding 102 Variants. What is Replication?

A new Depression study claiming 102 genetic variants has just come out (pre-publish).  I don't want to do an extended critique, so I will stick to a few main points:

The Good News Bible of Educational Attainment

In an effort to keep the "Educational Attainment" study relevant, we get yet more mileage from this polygenic risk score in another study.  It's a Plomin study, so you know where it's going, of course.  What strikes me most about this study is the absolute optimism and failure to consider than any of the findings can be anything other than proof of the genetics of "educational attainment," an absurd notion if you really turn off your filters for a second.  So let's go through it, a bit, shall we? 
Let's start with the opening sentence, which I think sets the scene for all of the rest that follows:

Ever increasing sample sizes and methodological advances in polygenic methods have made it possible to powerfully predict complex traits such as cognitive abilities without knowing anything about the causal chain between genes and behaviour. 

The question, of course, here, is what you are actually predicting? 

More Risk-Taking genetics

I will make a quick point related to this study:
Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression (Strawbridge, et al.).

The study notes 8 novel loci for this so-called "risk-taking behavior" (diagnosed by asking people one question: “Would you describe yourself as someone who takes risks?”), as well as noting "...two replicated previous findings."  My quick point is that the 2 "replicated" SNP's were from a previous study by the same author using the same UK Biobank dataset (which has expanded since the last study from a few months ago).  Obviously, you would expect some "replication" when using overlapping datasets.

In short, no independently replicated SNP's from previous studies of this ilk, and some of the SNP's, even bolstered by using some of the same data, were not replicated.  Moreover, no independent analysis of the new data, which was simply folded into the old study in a meta-analysis type of format.  Again, in an attempt to bolster N, the study did not look at the new data independently.  

I might add to this critique when I've had more time to examine it in detail. 

It's Already Eugenics.

Over the past several years, I have spent  time taking on studies related to the genetics of mental illness, IQ, personality traits, etc.  I have done so for a few reasons, but largely to counter what I think is, effectively, a reductionist mindset that pervades the scientific community and, by extension, society at large, leading to a kind of eugenic attitude towards society's problems.  I believe that this is quite harmful.  My general approach has been to attack the studies directly, which have historically been relatively easy to pick apart, even for someone who does not work directly in such research.   It was my view, and still is, that the "findings" in these studies are not what is generally being suggested (genes for the traits noted above). 
Up until recently, these studies repeatedly failed to replicate at all, and the mantra from scientists was that they just needed bigger databases.  I had hoped this would not be the case, but I can see now that as the databases are getting into the millions, it appears that they are starting to get some associations that are relatively consistent (at least within specific groups). (Update: Please see Addendum 2 below.  it is still unclear to me to what extent there is replication).
What these associations mean,  of course, is open for debate and speculation.  I am of the view that they don't really have anything to do with the actual traits and are probably some form of population stratification, but even if that is the case, it does allow for a bit of statistical predictive capability.  In my opinion, this  minor predictive success will soon become asymptotic, but that alone is enough to fuel years of these studies, striving for better and better predictability.   Nevertheless, this puts me in a rather difficult position.

Progressives should not "Embrace the Genetics of Education." Nor should anyone else.

A new study (which I hope to critique in the next week or so), has all the usual suspects excited and touting it as some conclusive proof of their genetic assumptions.  I would like to specifically address this NY Times Op-Ed from Paige Harden, PhD.  I'm sure she feels that it is well-intentioned and focused on the best interests of society, but that is exactly the problem.  What is really happening in this piece is the use of genetic assumptions to justify a world view.  Let's start with the title:

Why Progressives Should Embrace the Genetics of Education

Before we even start, think about that for just a moment. "The genetics of education." 

Are Polygenic Risk Scores Just a Measure of Population Stratification?

This preprint article  came out recently regarding GWAS results for height.  It created a bit of a stir amongst scientists involved in this kind of research, as it questioned the validity of previous, significant genetic associations for height.  This got me to thinking about the current Holy Grail of  GWAS researchers: The polygenic risk score.  I believe that their conclusion throws the whole concept into question.  Let me explain...

Genes for loneliness, health club attendance, bar hopping and churchgoing, all in one study!

I am attempting to critique this study:

Elucidating the genetic basis of social interaction and isolation (Day et al.)

There are many directions I can go with such a critique.  The most appealing and easiest, would be to mock it with a couple of quick quotes and be done with it.  Then, I think to myself, are there people out there that take a study like this seriously?  And, of course there are a lot of people who take a study like this seriously.  

I'm hoping, though, that there are a few scientists who have been holding onto these GWAS studies as some sort of proof of all kinds of mental constructs, who might have a bit of a crisis of confidence when reading something like this.  Perhaps they would like to dismiss this as an outlier, or misguided in some way.

Here's where they have a problem.  Because, this study was done by the book.  It has all the elements used to prove that there are genetic associations for these traits, just as studies are done to find associations for IQ, mental disorders, and personality traits.  So if you are touting GWAS studies related to any of these traits, you need to explain why your study is good and this one is ridiculous, or you need to embrace this ridiculous study.  There is no in between.

With that in mind, I will go through how this study follows the same formula as your cherished studies and you can decide which side of the health club attendance gene fence you sit on.

More Evidence That No One Knows What Is Going On.

This piece: 

"Theory Suggests That All Genes Affect Every Complex Trait," shows how little has been gleaned from all of these GWAS studies.  They simply have no idea what or how genes affect complex traits.  They have no way of explaining high heritability through this mechanism, either.  Here's an excerpt from the title:

The more closely geneticists look at complex traits and diseases, the harder it gets to find active genes that don’t influence them.

Another way of saying this is that they are all false positives.  The most ridiculous part of this is that they advocate for even larger GWAS studies to figure this all out.  C'mon.  Admit it's a failure.  Move on...

The Bell Tolls for Thee, GWAS

It appears from this paper, that a new wave of skepticism is starting related to GWAS studies.  The fact that the studies are largely false positives is not stated overtly, but you can feel some doubt from the believers.

Some excerpts:

GWAS are fast expanding to encompass hundreds of thousands, even millions, of patients (see 'The genome-wide tide'). But biologists are likely to find that larger studies turn up more and more genetic variants — or 'hits' — that have minuscule influences on disease, says Jonathan Pritchard, a geneticist at Stanford University in California. It seems likely, he argues, that common illnesses could be linked by GWAS to hundreds of thousands of DNA variants: potentially, to every single DNA region that happens to be active in a tissue involved in a disease.

Can you almost hear them saying "false positives"?

Here's another interesting excerpt:

Are you Hangry?...

I hesitate to go after studies that have a ridiculous enough premise to start with, but after critiquing GWAS studies, they are all starting to sound a bit ridiculous and I think we have a bit of a slippery slope, where there is this idea that a gene can be found for just about anything you can conceive of.  Do you like raisins?  Maybe there's a gene for that.  Do you think elephants are simply beautiful?  Perhaps it's a gene that makes you think that...
So here is a real study that was done to determine whether there is a gene for getting "hangry."  What is hangry, you might ask?  Well, of course it is the propensity to get angry when you get hungry.  Get it?  Hangry...   Here is a link to it so that you don't think I'm making it up
In any case, I'll take it on...

Another GWAS meta-analysis that suggests replications when the opposite is the case

"Since the discovery of general cognitive ability (or ‘g’) in 1904..."  (When I read a sentence like this, I am already a bit leery of what will come next.)

This critique is for the following study: 

Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function.  Gail Davies, et al.

This study is a meta-analysis of several studies I have already critiqued, here, here and here, as well as some new cohorts.  If I understand correctly, the new ones are the CHARGE and COGENT cohorts, but  in any case, it does not appear that any of the new datasets were ever studied independently related to cognitive ability and were simply added to the N of the meta-analyis.  I have a problem with this, which hopefully will become obvious as you read this critique. 

GWAS Catalog For Life!

Steve Pittelli <stevepittelli@gmail.com>	6:51 PM (19 hours ago)
to gwas-info

Hello there,
I was wondering what your policy is, regarding GWAS associations that are not subsequently replicated or are in some way refuted?  Do you ever remove them from the catalog or otherwise make a note of this?
Thanks,
Steve Pittelli

Annalisa Buniello <buniello@ebi.ac.uk>	9:29 AM (5 hours ago)
to me, gwas-info

Dear Steve,

Many thanks for your email and your interest in the GWAS Catalog.

As we also describe in our extraction methods https://www.ebi.ac.uk/gwas/docs/methods, individual SNP-trait associations identified in eligible publications are included in the Catalog only if they are statistically significant  (SNP-trait p-value <1.0 x 10-5) the in the overall (initial GWAS + replication) population. 

But if by not subsequently replicated you mean an association that is later found to not be valid, then the answer to your questions is no. We don’t remove the SNPs from the Catalog once they have been extracted from a previous publication that reported data from the original GWAS.

I hope this answers your question, but please don’t hesitate to contact us if you have further queries or comments on the GWAS Catalog.

Best wishes,

Annalisa

Annalisa Buniello, PhD
Scientific Curator
Open Targets and GWAS Catalog

Hard to argue with this...

"My prediction that GWAS studies would turn up many replicable genetic hits for IQ "within 10 years" was correct. <- My last tweet to you. Bye."

-Stuart Ritchie, with a very thoughtful retort to my contention that GWAS studies are likely all false positives (shortly after calling me a "crank"). At least he actually responded. Notice, by the way, that he said, "replicable" and not replicated. Cute, that.

Addendum:
"Finally, it is also possible that, although specific loci reached genome-wide significance in particular studies, there are false positives, highlighting the importance of well-powered replication studies."

From a study published two weeks later and co-authored by Stuart Ritchie.

A Quick Review of a Dyslexia GWAS study claiming two significant loci

I will try to trim this review down to its barebones for an easier read, but welcome any comments or clarifications.  The study in question can be found here.

Genome Wide Association Scan identifies new variants associated with a cognitive predictor of dyslexia 

The study is on a much smaller scale, with only a few thousand cases, so one might expect fewer false positives.  In this case, likely we have two.