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