Comment by gwern | Hacker News Reader

Comment by gwern | Hacker News Reader

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Nope. You're wrong. Where do you think your MRs or your sibling comparisons are coming from? You're not getting anywhere with weak instruments from a few significant hits. You're also wrong that the only thing of value is inferring "how genes work", and that is the sort of extremely blinkered mechanism-centric attitude which blinded people to GWASes working, because gosh, it would be awful if polygenicity was true, because how would we build any 'scientific theories' on this? (Cue Turkheimer.) And yes, those PGSes are useful for all sorts of things like selective sweeps, enrichments, and clinical instruments, because of incremental validity. (By the way, what does '15% heritability' refer to? I sure hope that, since you're claiming to be an expert here, you aren't confusing heritability with PGS power, like so many supposed human geneticists insist on doing...)

I didn't say GWASes were useless, just that it's absurd to consider them to be a 'revolution'. The actual revolution would be second- and third-generation sequencing which enabled GWASes and a bunch of much more useful things. GWAS is, in effect, just a bunch of correlations. It's just the very starting point to an actual scientific analysis, because 'you have to start somewhere'. If you don't go beyond and investigate, you're not doing science. Everyone in the genomics community agrees to this, and literally every paper that investigates the causes of genetic diseases goes in the introduction like 'GWASes sure look nice but we still have no idea how things work with them so in this paper I present a method to do...' I notice you failed to address many of the spurious correlations drawn by the GWAS bot or the A. thaliana vs. GDP prediction. That it doesn't raise any red flag to you doesn't speak well as to your ability to approach the field of genomics.

>You're also wrong that the only thing of value is inferring "how genes work"

Yes it is, that's literally what genetics is about. Otherwise you're back to making a bunch of correlations. If you want a deep understanding of disease, design effective drugs, or even do proper gene editing, you have to understand what genes do. It seems ridiculous to have to say it.

>By the way, what does '15% heritability' refer to?

It is what we in the less-rationalist circles refer to as a 'joke'.

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