I apologize for misinterpreting your response as sarcastic. Why do you believe that PCA successfully captures all the relevant population structure? Probablist

I apologize for misinterpreting your response as sarcastic. Why do you believe that PCA successfully captures all the relevant population structure? Probablistically, it's a Gaussian linear model... no reason to expect allele frequencies to follow that. If that were the case, methods like coalescent theory would be unnecessary. Why do you believe that high genetic correlations between cohorts is sufficient to ensure safe inference from GWAS meta analysis? These are tiny effect sizes, and the argument is essentially that the correlations with intelligence measurements are statistically significant. Unless you believe that your null model is an otherwise entirely accurate reflection of how the data is generated, of course you're going to see spuriously significant results in huge samples. I'll respond to your other points when/if I catch up on the literature. I'd be grateful if you could link the papers about the enrichment sets and tissue expression results.