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On the Impossibility of Interaction with Simulated Agents 2022-01-13T17:50:25.987Z

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Comment by Walkabout on Should I delay having children to take advantage of polygenic screening? · 2021-12-20T15:38:58.212Z · LW · GW

One issue nobody has raised yet is the effects of structural racism.

The GWAS studies used to create the polygenic risk scores generally have a very pronounced sampling bias towards people of European ancestry. See for example the GWAS Diversity Monitor, which is a dashboard meant to monitor the sampling practices used by GWAS studies. In addition to selecting people to sample by ethnicity, an accepted practice is to look at the genomes after sampling and try to identify and exclude "ethnic outliers".

If you or your partner don't have ethnicities that would make your genomes look typical among the samples used to train the scoring algorithm, it's an open question whether any particular score instrument is going to be usefully predictive for you or your potential child. See for example Generalization and dilution of association results from European GWAS in populations of non-European ancestry: the PAGE study, which found that, while many GWAS hits generalize from a very restricted sample, a substantial fraction don't. See also Current clinical use of polygenic scores will risk exacerbating health disparities, which discusses polygenic risk scores in particular, and their accuracy falloff when used on people who the score developers would have excluded from their training set.

Note also that even the papers complaining about this problem are still breaking down their results by very abstract discrete dimensions like "5 continental populations", which sweep a lot of people under a very large rug. If you and your partner have different ethnicities, you get to be on the wrong end of fun lines like this one, from that last paper:

Related to stratification, most PRS methods do not explicitly address recent admixture and none consider recently admixed individuals’ unique local mosaic of ancestry; further methods development is needed.