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[Adrian]

How population stratification led to a decade of sensationally false genetic findings

On parlait du livre de Reich sur l'autre topic :

 

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This height example might seem far-fetched, but pretty much exactly what I described actually happened, and it led to a decade-long mess where the field was convinced that Europeans had undergone rapid natural selection on height (and other phenotypes correlated with height like … head circumference) only to learn in 2019 that it was all or nearly all explained by stratification (see Berg et al. and Sohail et al. eLife; or press coverage that concludes “this is a major wake up call … a game changer”). But prior to learning this error, the possibility of selection on head circumference got people speculating what else about the head could be under rapid recent selection. That speculation included an famous opinion piece by esteemed population geneticist David Reich raising concern that genetic analyses may soon reveal substantial biological differences among human populations on traits like intelligence; differences that we as a society were unprepared to grapple with1. Naturally, in some circles, Reich’s cautious and circumscribed warnings that we may eventually find challenging genetic differences were read as a kind of Straussian message, a cryptic admission of precisely the “racist prejudices and agendas” Reich was attempting to head off (and, I should note, that he spent another two chapters in his book explicitly denouncing). Snippets from his editorial were further stripped of context, sometimes reworded entirely, and became meme fodder for open racists: Harvard’s superstar geneticist is secretly on our side, the truth about the inferior races will soon be revealed. And these memes continue to get passed around today, more than five years since the motivating height result was shown to be an artifact (in a paper on which Reich is a corresponding author no less). All of which is to say that poor control for population structure can have, well, some pretty big consequences.

 

 

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For educational attainment, they find no significant genetic correlation with number of children and a point estimate at roughly zero (though with large uncertainty). But for Cognitive Performance / IQ scores, they do find a significantly positive genetic correlation with number of children. That’s right, positive. The same variants that appear to increase cognitive performance also appear to increase the number of offspring (implying, if all of the model assumptions hold up, that higher cognitive performance may actually be under some amount of positive selection). Not only is this the complete opposite of what has been observed in prior analyses from polygenic scores, it also runs counter to the environmental observation. Have we stumbled on a paradox? Not quite, as Beauchamp also noted in a commentary about his own findings:

First, there is nothing paradoxical about my findings. Phenotypes arise from the interplay of genetic and environmental factors, and environmental factors can induce phenotypic changes that run counter to those induced by natural selection. Although the slightly lower fertility of individuals carrying genetic variants associated with higher EA [educational attainment] implies that natural selection has been slowly favoring lower EA, countervailing cultural, economic, policy, and other environmental factors are almost certainly responsible for the vast increase in average EA observed in the past century.

It turns out that this view may have been conceptually correct but directionally wrong. When stratification is better controlled, there appears to be no direct genetic relationship between EA and fertility. And if natural selection is acting at all, it is slowly favoring higher Cognitive Performance. This is not yet a definitive answer — the Tan et al. / LDSC results still come with substantial statistical uncertainty and model assumptions — but it is clear that as we do a better job of addressing stratification, the results can change completely.

 

[Adrian]