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Paper rejected by Intelligence with comments

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."
'Diversifying selection is most commonly measured using the Fst index at or around single loci (Holsinger & Weir, 2009).' This needs to be expained further.
'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.

Attached Files
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Since Intelligence is not allowing me to do this, I am preparing a response to these reviews, will post them here and then send them to the Editor asking to forward it to the reviewers.
re: "I recommend the rejection of this manuscript without opportunity for revision. It does not meet the very high standards..."

Who was the ******* that wrote this comment?
(2016-Jan-03, 23:36:16)Chuck Wrote: re: "I recommend the rejection of this manuscript without opportunity for revision. It does not meet the very high standards..."

Who was the ******* that wrote this comment?

One of the ******** that review for Intelligence. Unfortunately their crippled system is not double blind, so the reviewers know the identity of the authors, but the authors don't know who the reviewers are. I can tell right away that it's a new reviewer, that's to say nobody that had reviewed any of the papers that I had previously submitted to Intelligence. New editor (Richard Haier), new reviewers I guess, especially if the editor doesn't like your paper. Anyway, I agree with you that the attitude of that reviewer should not be allowed. It's bad for science.
Applying Double Standards to ‘‘Divisive’’ Ideas

But it may not be what the reviewer had in mind. But many people apparently have ideas of that kind.
New Editor of intelligence has changed the rules. I had a paper where both reviewers were nice and kind of positive of the submission. But the paper got rejected by Dr. Haier.
(2016-Jan-05, 17:17:20)salahodjaev Wrote: New Editor of intelligence has changed the rules. I had a paper where both reviewers were nice and kind of positive of the submission. But the paper got rejected by Dr. Haier.

Hi! Would you mind posting the reviews on here on a separate thread?
(2016-Jan-05, 17:28:03)Duxide Wrote:
(2016-Jan-05, 17:17:20)salahodjaev Wrote: New Editor of intelligence has changed the rules. I had a paper where both reviewers were nice and kind of positive of the submission. But the paper got rejected by Dr. Haier.

Hi! Would you mind posting the reviews on here on a separate thread?

Seems things gone awry at Intelligence. I second Duxide. I would like to read the paper too (even sent by mail or whatever).
I think I know what happened. Let's start with the basics: First, this research is based on data from the Social Science Genetic Association Consortium (SSGAC). This is a major enterprise that has produced the Rietveld et al 2013 study and most of what came after it. It is a continuing enterprise, although I do not know what exactly their current projects are. You can check their website, where they have basic information.

Second, this research is leading to a paradigm shift in the social sciences if there has ever been one. Even the first studies with educational attainment genes are already showing that these genes are associated with family advantage and social mobility, basically confirming Herrnstein & Murray: B.W. Domingue et al. (2015): Polygenic influence on educational attainment: New evidence from the National Longitudinal Study of Adolescent to Adult Health. AERA Open 1(3): 1-13. These authors, from major research universities, did not report differences between white and black Americans although they reported results from samples of both separately. Davide's work shows why they did not report the race differences. His results, if reproducible, have profound implications for development economics by showing which developing countries will catch up and which ones won't. A field that has no published results yet is the study of ancient DNA. If it turns out that the rise and fall of civilizations (including our own) was associated with subtle changes in allele frequencies for educational attainment genes and/or conservatism genes, the history books will need to be rewritten. In other words, the people organizing the SSGAC deserve a Nobel Prize if their work is successful, and they know it.

Now back to the Intelligence editors. To whom do you think will they send a paper like Davide's? If I were editor of Intelligence, I would try to track down one of the SSGAC people and send it to him. That's what Haier did, and he did the right thing. Look at Reviewer #1. He is obviously an expert in the field, thoroughly familiar with the literature and the methods. Most of his criticisms are hollow, as far as I can see with my limited expertise. It is also obvious that for the important result, you don't even need the higher maths. All you need to do is look up the allele frequencies at 1000 Genomes and then compare them across populations. The rest is mainly (though not entirely) the "look how smart I am" game that career academics have to play to impress journal editors, funding agencies and tenure boards. What is important is that Reviewer 1 is not one of the run-of-the-mill activists whose aim is to obstruct science. Those are stupid and devious. Reviewer 1 is not stupid.

Now put yourself in the place of the SSGAC leader. He is trying to bring dozens and perhaps hundreds of scientists together to first meta-analyze existing literature and then organize new studies to corroborate (or refute) the initial findings and extend the original results. This is an open-ended enterprise that requires millions of dollars for studies that involve hundreds of thousands of subjects, each genotyped with a $200 DNA chip or with a genome sequence costing about $2000. You see the problem. If results like Davide's are broadcast thoughtlessly and everyone realizes what the likely outcome of this research will be, what will be the response? The risk is, simply, that regulators and administrators will get alarmed and the whole research will be shut down. Scientists will no longer want to collaborate with the SSGAC for fear about their funding and their careers, and the whole enterprise will collapse. Even free access to genomic databases like HapMap and 1000 Genomes will be in jeopardy because there will be calls for restricting access to vetted scientists from established labs (i.e., those in vulnerable careers), in order to prevent "irresponsible" use of genomic data. This is the reason why reviewer #1 did the sensible thing: prevent the publication of this paper.

Eventually, this whole SSGAC enterprise makes sense only if people do accept the results of the research with all its implications. This will not be possible if we hide the results and thereby prevent public debate altogether. This strategy would only enhance the cynicism about social science that is rampant already and that is one reason why the SSGAC was started in the first place. Squeezing the genie back into the bottle is not an option, not after we already have the first replicable associations and the population genetic data for the SNPs are still publicly available. What we need is a consensus of sorts that eventually, people should know the truth whatever it may be, that they should accept it as part of their worldview, and that they should use it responsibly. But strategy-wise, the absolute priority for now must be to avoid anything that would jeopardize ongoing research in the field and access to the data it produces. Therefore I tend to defer to the judgment of Reviewer #1, who is more familiar with the situation than any of us.

Next we have to spell out the nature of the opposition to this research. I mentioned before that run-of-the-mill anti-science activists are not only stupid but also devious. Their basic problem is that they, personally, are unable to accept people who are significantly different from themselves. Academics, for example, despise people who are less intelligent than themselves, and generally, everyone who does not conform to the values and beliefs of the white middle-class male is an abomination: women who want to raise children rather than being engineers, blacks living in their own subculture, working-class people with their own peculiar values, and generally everyone less successful in life than themselves. What makes these people offensive is that they do not recognize their inability to accept diversity as a moral deficiency, and that they falsely accuse others to share this deficiency. That's why we can classify them as deviants, and that's what explains the unethical practices that they commonly employ and that scientists fear so much.

The results that come out of the SSGAC enterprise, including Davide's, will not be ready for prime time unless people realize that their implications are not as heinous as they have been told they would be. The problem is to convince them that most people (other than politically correct anti-science activists) are perfectly able to deal responsibly with biodiversity where it really exists. Why should it be necessary to re-educate all women into male roles? Let them choose for themselves (according to their testosterone level, I guess), whether they prefer traditional male or female roles! If some people are not quite as bright or ambitious as others, what decent folks will do is not to blame them for their shortcomings, but to make accommodations for the whole spectrum of genetic disability that we have in the population. After all, everyone of us is somewhere on this spectrum. What science tells us is that all human genomes are junk yards with thousands of suboptimal mutations that are there for no better reason than that they are not bad enough to prevent reproduction. And if we know the genes that put individuals and perhaps entire nations at a disadvantage, it's up to us to maintain or eliminate these disadvantages. Why eliminate only environmental disadvantages with measures such as mandatory schooling and social welfare? Why not eliminate genetic disadvantages as well? Simply select the right embryos, and edit their genomes with CRISPR-CAS or some other system!

So what should the strategy be? Probably the best strategy is to publish the results in places where they are public (not a subscription-based journal like Intelligence), but not sufficiently visible to hit the fan. Don't attract journalists to put sensationalist reports in the popular press! This would jeopardize ongoing research. The authors of the AERA Open paper pretty much followed that strategy. At the same time, start a debate on suitable websites about the implications of biodiversity. Discuss the constructive implications of belief in biodiversity. For starters, gay-bashing bigots generally insist that there are no gay genes but that homosexuality is a lifestyle choice, while supporters of gay rights (according to surveys) tend to believe that gays are "born that way." Do people realize that? Perhaps they need to be told. People who don't blame bad outcomes on genes because they are told there are no genetic differences will usually end up blaming victims. See if such arguments have any traction at all. References to the research results should be made first sparingly and then more frequently. In a few years, if the results and conclusions of Davide and others hold up and get stronger support, we can get bolder and simply say that this is nothing unusual and that it has been known for several years already. It's somewhat like with genetically engineered food. In Europe, violent opposition to genetically modified food was a powerful movement lasting for several decades. In America, they introduced genetically modified food without making people aware of it, and then told them: "So what? You have been eating that stuff for many years, and nothing bad has happened." This is the kind of strategy that can get Davide's research and other results like this accepted without backlash.

It is of course possible that the outcome of that debate is that people are indeed unable to accept truly existing biodiversity without having shitty attitudes. In that case, my recommendation is to forget about science, collect money to buy a bunch of nukes from corrupt army officers, and donate them to ISIS.
Good post, Gerhard. Perhaps it is a wiser choice to publish this kind of research in less read journals for the time being. A problem with that is that Wikipedia editors will then refuse to update the articles (since wasn't published in major journals). Some people are concerned about that. http://humanvarieties.org/2014/07/24/adv...a-editors/
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