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:

In a paper published in Cell on 15 June¹, Pritchard and two other geneticists suggest that many GWAS hits have no specific biological relevance to disease and wouldn’t serve as good drug targets. Rather, these 'peripheral' variants probably act through complex biochemical regulatory networks to influence the activity of a few ‘core’ genes that are more directly connected to an illness.

The problem with that is that these "core" genes should be hits in a GWAS.  So theoretically,  they should be the most obvious hits and no such thing has been found (in any GWAS for any trait, as far as I know).  I like how it closes, too:

But Aravinda Chakravarti, a human geneticist at Johns Hopkins University in Baltimore, Maryland, hopes that the paper will challenge what he terms a “cowboy attitude” in genomics research that emphasizes collecting ever more genetic associations over understanding the deeper biology behind them. “This is a nice paper simply because it’s going to kick people in the shin, which, as scientists, we need from time to time.”

I will continue to do my part to kick them in the chins...