There are so many studies coming out noting population stratification issues that it is hard to keep track. This is an interesting preprint looking at CAD and BMI:
Fine-scale population structure confounds genetic risk scores in the ascertainment population
From the Abstract:
we investigated the accuracy of two different GRS across population strata of the UK Biobank, separated along principal component (PC) axes, considering different approaches to account for social and environmental confounders. We found that these scores did not predict the real differences in phenotypes observed along the first principal component, with evidence of discrepancies on axes as high as PC45. These results demonstrate that the measures currently taken for correcting for population structure are not sufficient, and the need for social and environmental confounders to be factored into the creation of GRS.
One interesting aspect of this study, I think, is that it highlights how it can be necessary to have a good working knowledge of the population you are studying. This plot is striking in that respect:
This was confined only to white European descent, but still had this kind of stratification. A larger point here is that more and more pop/strat issues arise, many of which were not accounted for in earlier studies and perhaps should lead to corrections. Moreover, for those doing GWAS in the future, particularly in the UK BioBank, it is worth having a bit of skepticism that at least some of what you are seeing is pop/strat that has yet to be recognized.
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