Rex Kerr
1 min readMar 24, 2023

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This is a splendid summary! Much more accessible than the typical review article, even to someone who knows a fair bit about human genetics.

The only thing I'd want to add is that a PRS is usually* a substantial underestimate because it is hard to detect the contribution of many weak alleles. So it's a testament to the polygenicity that the PRS falls well below the heritability, but it doesn't necessarily mean that the polygenic picture isn't the whole story. (I'm also a little bit surprised that you mentioned CNV and not epigenetics--not that either is that robustly verified right now from what I've seen.)

Anyway, height has a similarly large gulf between heritability and variance explained by polygenic score; it's kind of par for the course with the sample sizes we tend to have these days.

(* Technical detail: uncorrected population stratification can lead to large overestimates. So we need to be tentative here, too. Even with height: https://elifesciences.org/articles/39702.)

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Rex Kerr
Rex Kerr

Written by Rex Kerr

One who rejoices when everything is made as simple as possible, but no simpler. Sayer of things that may be wrong, but not so bad that they're not even wrong.

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