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Divergent selection on height and cognitive ability: evidence from Fst and polygenic scores

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Author
Davide Piffer

Title
Divergent selection on height and cognitive ability: evidence from Fst and polygenic scores

Abstract

Tests of selection based on population differentiation were performed on two highly polygenic traits important for success and satisfaction in life: height and educational attainment (EA).

Polygenic scores (PGS) of EA and height, computed across three public genomic databases revealed differences between populations (1000 Genomes, HGDP, gnomAD) that matched the average IQ and height of ethnic groups (r ~0.9).

A moderately strong correlation between latitude and EA PGS (r= 0.68), significantly deviating from the correlations of random SNPs, suggests the implication of climate (seasonality or winter temperature) for selection on cognitive abilities.

The global Fst index revealed population differentiation at height and EA loci, significantly deviating from random SNPs.

Substantial LD decay between Africans and Europeans was found (r= 0.6) but there was no correlation between Linkage disequilibrium (LD) decay and population differences in polygenic scores (r= 0.015, p= 0.45) for EA, and slight inflation of height PGS difference due to LD decay (r= -0.04, p= 0.0315).

 implying that LD decay does not produce a bias in polygenic scores of non-European populations. Finally, it is shown that PGS differences are more sensitive to SNP significance than Fst, reflecting the major limitations of Fst as an index of selection.

 

 

Keywords
IQ, education, polygenic selection, gwas, polygenic scores

Supplemental materials link
https://osf.io/6dvfc/

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Paper

Reviewers ( 0 / 0 / 3 )
Reviewer 1: Accept
Reviewer 2: Accept
Reviewer 3: Accept

Sun 31 Jan 2021 09:39

Discussion: You find that European-African polygenic scores for educational attainment differ by more than 1.5 standard deviations. Some readers may find that strange because the actual difference between black and white Americans today is barely one standard deviation, and differences in educational attainment are even less. 

There are several possible reasons:

- European admixture in African Americans, about 20%

- Differences in cognitive ability among the West African groups who are ancestral to African Americans. Some, like the Igbo of Nigeria, seem to be high achievers

- Polygenic scores are based on alleles associated with educational attainment. As such, they reflect not only cognitive ability but also the willingness to follow classroom discipline, i.e., do what the teacher tells you to do, keep quiet in class, etc.

I'm not sure about the statement "differences in educational attainment are even less." First, educational attainment statistics are biased toward students who are attending school (and who are not suspended or truant). So there is some sampling bias. Second, there has been a lot of pressure on American school boards to equalize educational attainment. 

Author
Replying to Reviewer 2
Replying to Forum Bot

Authors have updated the submission to version #14

Good work. Should be accepted after some very minor revisions.

Some specifics:

Abstract, 5th paragraph:

Substantial Linkage Equilibrium (LD) Decay between Africans and Europeans …

This should be linkage disequilibrium, not linkage equilibrium.

 

Last sentence of abstract:

Finally, it is shown that PGS differences are more sensitive to the significance of GWAS loci than Fst,…

Better: Finally, it is shown that PGS differences are more sensitive than Fst to the significance of GWAS loci

Page 2, last sentence of first complete paragraph: …, which can inflate signals of selection due to co-variance between genes and the environment. Is this current or ancestral environment with which the genes covary?

Table 1: Are these coefficients from regression models with African as the omitted control? This should be mentioned.

Figure 6: I notice that EA polygenic scores for African American and Barbados are almost as low as those of the West African groups, although they have 20% - 25% European admixture. If this is not a fluke, it could mean that most of the admixture-related gains were eaten up by dysgenics. Perhaps something on these lines could be mentioned in the discussion.

Figure 15 is missing a proper heading.

Discussion: You find that European-African polygenic scores for educational attainment differ by more than 1.5 standard deviations. Some readers may find that strange because the actual difference between black and white Americans today is barely one standard deviation, and differences in educational attainment are even less. Such apparent discrepancies could possibly lead people to conclude that therefore there must be something wrong with the genetic results. Can you offer an explanation for this apparent inconsistency? What looks most obvious to me is that the polygenic scores include only the effects of common polymorphisms but not those of rare variants that are mostly subject to mutation-selection balance (aka “genetic garbage”). While polygenic scores reflect the cumulative effect of selection over more than 50,000 years, the genetic garbage is of more recent origin. If recent selection for educational attainment (last few centuries) was the same in different populations, the genetic garbage will be about the same. Therefore, the total genetic difference will be less, and possibly far less, than the 1.5 SD difference in polygenic scores. So, the large size of the PGS difference would indicate that genetic population differences originated through early selection rather than very recent selection.

See my previous reply.

Lee et al. (2018) is missing from the list of references

 

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Author has updated the submission to version #16