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As you know, this blog moves at internet speed, not the glacial creep imposed by academic publishers, with their lucrative frustration of intellectual discourse. No sooner do I write about the work of Piffer, and his use of the new findings of Sniekers et al. (2017) than a senior author on that latter paper, Prof Danielle Posthuma, writes to me about Piffer’s calculations.
Piffer uses genetic variants that explain differences between individuals in a European population, to explain differences between European and non-European populations. Our results are not informative in explaining between population differences. (see e.g. http://www.cell.com/ajhg/fulltext/S0002-9297(17)30107-6).
There are basically three issues:
1 Causal alleles need not be the same in European and non-European populations. We do not know that now. Piffer implicitly assumes they are, but there is no evidence that the alleles we found can also explain part of the genetic variance in non-European populations.
2 Linkage Disequilibrium structure and allele frequencies are not necessarily the same across different populations, and therefore beta’s estimated in one population cannot be transferred to another population.
3 The only thing Piffer shows is that alleles that have been associated with educational attainment or IQ in an European population have different frequencies in other populations. This is true for a lot of alleles, irrespective of whether they are associated with Educational Attainment/IQ and is due to historical/geographical divergence, and thus does not have any relevance in explaining between group phenotypic differences. If our discovery sample were to be non-European we would probably also predict the European population to have a lower intelligence, simply because the alleles that explain differences with the non-European population may have a lower frequency in the European population, due to historical reasons. Thus, that prediction is meaningless for explaining between group differences.
Also, if we would apply the same to GWAS results for height, we would predict Africans are much shorter than Europeans, which is not the case. This is a very deep-rooted misunderstanding and misuse of GWAS results, and especially unfortunate for intelligence and the racial issues in that context.
Let me give you my lay responses.
Of course, the alleles need not be causal in the same way in Europeans and non-Europeans. Several recent papers have suggested that they are different. I find that rather odd, but there could be many ways to wire a brain.
The linkage disequilibrium structures do not have to be the same, and are probably not the same.
You say that Piffer’s approach shows sample of discovery bias. However, he overcame my scepticism by having a random SNP control condition. Does that not work?
Prof Posthuma replied:
I have not looked at how Piffer created the random SNP set. However, I do not think the question is whether the method is good. The question is whether the outcome makes sense (and can be interpreted in the way he does), and that is where I think he goes in the wrong, as the within group (within EUR) variance is not informative for explaining between group differences.
That is as far as our conversation went at this stage, and I hope this helps in further comment and discussion.