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Paper rejected by Intelligence with comments

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I attach my latest submission to Intelligence. I considered that venue because that's where the previous paper dealing with the same issue had been published. Reviewer's comments are reported below. Since a discussion with the reviewers was forbidden by the editor (following reviewer #1's suggestion to reject without review), maybe such a forbidden discussion can take place in this open arena amongst people of all beliefs and backgrounds. SUBSTANTIAL contribution to the review can result in co-authorship.

Reviewer #1: I recommend the rejection of this manuscript without opportunity for revision. It does not meet the very high standards for demonstrations of natural selection acting to differentiate modern human populations that have been set by recent publications (Turchin et al., 2012; Robinson et al., 2015). Here I will only detail a few of the manuscript's shortcomings.

The authors do not address the possibility that the GWAS results of Rietveld et al. (2013) are contaminated by confounding (cognition- or education-affecting environmental variables that happen to be correlated with genetic variation). Although the original publications of the SSGAC deal with this issue to some extent, they do not come up to the standards set in the papers that I have cited in the previous paragraph. Furthermore, one research group with control of an extremely large family cohort is currently working on a manuscript documenting that years of education is subject to a very peculiar form of confounding. Until these results are published and well absorbed, any naive inferences regarding the basis of racial differences should be regarded with skepticism.

The authors also do not address the issue of ascertainment bias. A GWAS of Europeans is more likely to detect SNPs with high minor allele frequencies. The minor allele is usually the derived allele, and thus the use of SNPs ascertained to have low p-values in a GWAS of Europeans will lead to an overrepresentation of SNPs with high derived allele frequencies specifically in Europeans. If the derived allele tends to have a positive effect (as the authors claim), this is certainly an issue that needs to be carefully addressed.

True, it may be that ascertainment bias is less of an issue when all SNPs regardless of p-value are used to construct a polygenic score. But the extrapolation to non-European populations is still problematic because the accuracy of the polygenic score declines in such populations as a result of differing LD patterns (Scutari et al., 2015). An example will make this clear. Suppose that two SNPs in perfect LD in Europeans have quantitatively close positive reference betas. Now suppose that in a different population the SNPs are uncorrelated, the reference allele at the causal SNP has a somewhat higher frequency, and the reference allele at the tag SNP has a much lower frequency. Then the inference made from comparing the polygenic scores of the two populations is exactly the opposite of the truth. We can conclude from this that the use of polygenic scores to infer the causes of intercontinental differences requires much more care than given to it here.

Because stabilizing selection (favoring the "golden mean," as the authors put it) also eliminates genetic variation, higher dispersion of allele frequencies across populations is by itself not diagnostic of directional selection.

The fact that a large fraction of the enhancing alleles reported by Rietveld et al. (2014) SNPs are derived does not mean very much. First, as it is likely that many of the SNPs are not causal, the relationship between derived alleles at different polymorphic sites must be addressed. Second, even if it be assumed that these are the causal SNPs, it is not necessarily the case that an association between derived status and a positive effect points toward selection increasing the mean of the trait. Such selection can actually lead to the opposite association (between derived status and a negative effect) at certain allele frequencies.

A general comment is that the appropriateness of much of the hypothesis testing in this paper is difficult to judge. The stochastic model justifying a particular statistical test is usually unclear. Is the source of randomness inaccuracy in the GWAS estimates? The inherent stochasticity of evolution?

Robinson, M. R., Hemani, G., Medina-Gomez, C., et al. (2015). Population differentiation of height and body mass index across Europe. Nature Genetics, 47, 1357-1362.

Scutari, M., Mackay, I., & Balding, D. J. Using genetic distance to infer the accuracy of genomic prediction. arXiv:1509.00415.

Turchin, M. C., Chiang, C. W. K., Palmer, C. D., Sankararaman, S., Reich, D., GIANT Consortiu, & Hirschhorn, J. N. (2012). Evidence of widespread selection on standing variation in Europe at height-associated SNPs. Nature Genetics, 44, 1015-1019.






Reviewer #2: I found this paper extremely reader-unfirendly. Starting from the title - which is cumbersome, to the tables - which lack meaningful explanations and notes, to references to specialist concepts - that require much further explanaion for non-expert reader, to the general structure of the write up - the paper needs extensive revisions before it can be considered for publication for Intelligence.
The paper is full of poorly justified conlusions. For example, in the abstract, the author claims: 'Cognitive-enhancing SNPs were significantly enriched for derived alleles
(64%), that is human-specific mutations that originated after the split from the most recent common ancestor between humans and other primates.' However, the Derived vs ancestral alleles section on page 9 does not present the releavant analyses in details, and therefore the conclusion is not justified.
The paper is full of sentences that would require further clarifications for non-expert audience. For exampole: 'Differences in allele frequencies between populations can be created by directional selection when the strength and/or direction of selection on the phenotype differs among populations. In this case it is also characterized as diversifying selection, in contrast to stabilizing selection which tends to favor the "golden mean."
OR
'Diversifying selection is most commonly measured using the Fst index at or around single loci (Holsinger & Weir, 2009).' This needs to be expained further.
OR
'Some SNPs had opposite betas on the two outcome variables (yes/no college completion and total years of education).' This requires further discussion.

I could go on giving examples of unclear sentences, but I believe that the paper needs to be worked on- the author should consult with non-expert (in this specific area) intelligence researchers - to arrive at a clearer, more streamlined and better explained manuscript. All analyses require futher explanations, perhaps, with specific examples, that would talk the reader through every step of the analyses.


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Messages In This Thread
Paper rejected by Intelligence with comments - by Duxide - 2016-Jan-02, 21:11:10
RE: Paper rejected by Intelligence with comments - by Duxide - 2016-Jan-03, 13:54:54
RE: Paper rejected by Intelligence with comments - by Chuck - 2016-Jan-03, 23:36:16
RE: Paper rejected by Intelligence with comments - by Duxide - 2016-Jan-04, 00:49:50
RE: Paper rejected by Intelligence with comments - by Emil - 2016-Jan-04, 01:17:05
RE: Paper rejected by Intelligence with comments - by salahodjaev - 2016-Jan-05, 17:17:20
RE: Paper rejected by Intelligence with comments - by Duxide - 2016-Jan-05, 17:28:03
RE: Paper rejected by Intelligence with comments - by Meng Hu - 2016-Jan-05, 19:38:37
RE: Paper rejected by Intelligence with comments - by Gmeisenberg - 2016-Jan-06, 16:58:33
RE: Paper rejected by Intelligence with comments - by Emil - 2016-Jan-07, 01:25:29
RE: Paper rejected by Intelligence with comments - by Duxide - 2016-Jan-07, 20:42:50
RE: Paper rejected by Intelligence with comments - by Duxide - 2016-Jan-09, 18:29:56
RE: Paper rejected by Intelligence with comments - by Chuck - 2016-Jan-20, 18:51:11
RE: Paper rejected by Intelligence with comments - by Emil - 2016-Jan-09, 22:43:49
RE: Paper rejected by Intelligence with comments - by Duxide - 2016-Jan-09, 22:57:17
RE: Paper rejected by Intelligence with comments - by Duxide - 2016-Jan-10, 22:46:30
RE: Paper rejected by Intelligence with comments - by Tetrapteryx - 2016-Jan-11, 07:57:22
RE: Paper rejected by Intelligence with comments - by Duxide - 2016-Jan-20, 17:24:49
RE: Paper rejected by Intelligence with comments - by Tetrapteryx - 2016-Jan-23, 01:46:50
RE: Paper rejected by Intelligence with comments - by Duxide - 2016-Jan-23, 10:56:58
RE: Paper rejected by Intelligence with comments - by Chuck - 2016-Jan-23, 19:18:27
RE: Paper rejected by Intelligence with comments - by Chuck - 2016-Jan-20, 17:48:27
RE: Paper rejected by Intelligence with comments - by Emily - 2016-Jan-23, 01:27:13
RE: Paper rejected by Intelligence with comments - by Tetrapteryx - 2016-Jan-23, 21:33:51
RE: Paper rejected by Intelligence with comments - by mwang - 2016-Jan-24, 14:51:35
RE: Paper rejected by Intelligence with comments - by Emil - 2016-Jan-24, 21:11:43
RE: Paper rejected by Intelligence with comments - by Tetrapteryx - 2016-Jan-24, 18:44:13
RE: Paper rejected by Intelligence with comments - by General-Factor analyst - 2016-Feb-11, 02:08:31
RE: Paper rejected by Intelligence with comments - by Duxide - 2016-Feb-11, 15:52:22
RE: Paper rejected by Intelligence with comments - by General-Factor analyst - 2016-Feb-11, 16:55:30
 
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