Wednesday, July 22, 2020

Another Paper Related to Pop Strat issues for GWAS

Another study discussing pop strat issues:

Demographic history impacts stratification in polygenic scores

Points out more issues with population stratification:
We show that when population structure is recent, it cannot be fully corrected using principal components based on common variants—the standard approach—because common variants are uninformative about recent demographic history.
They further note some limitations with sibling based studies:
While sibling-based association tests are immune to stratification, the hybrid approach of ascertaining variants in a standard GWAS and then re-estimating effect sizes in siblings reduces but does not eliminate bias. 
As I've argued previously, the "immune to stratification" point is not necessarily true secondary to factors like varying ages of the siblings and selections biases of the databases. Nonetheless, if using sibling studies  "reduces but does not eliminate bias," and they are bringing the variance explained down to 2 or 3 %, then arguably they are scraping along near the null. So, far from showing that some of the variance explained is retained in sibling studies, it might suggest that there is no real genetic component found.

Finally, it's worth pointing out that despite the growing number of studies showing pop/strat issues in the UK Biobank and other such databases, no one has taken it upon themselves to reevaluate their previous, published GWAS results in light of this. It's as if they are grandfathered in.

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