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Martie 19, 2017

UPDATE 03.05.2017

Michael Woodley & Davide Piffer (2017) published in bioRxiv a very interesting study, comparing polygenic scores on educational attainment of today and Bronze Age samples. They demonstrated a positive selection on intelligence, but they believe they demonstrated the increase of the genotypic intelligence of Europeans since Bronze Age. Their results rather demonstrate a decrease of the genotypic intelligence during last 4,000 years.

The most powerful GWAS on educational attainment (Okbay, 2016) found 74 common SNP that favor high-IQ (equating the educational attainment with the intelligence). The average effect of each of these SNP is 0.02% of variance and 0.02 SD of educational attainment (Okbay, 2016, Extended Data Figure 2). But 1 SD of EA equates with 3.8 IQ points (Kong, 2017), hence the effect of each SNP is 0.02 x 3.8 = 0.076 IQ points. In aggregate, these 74 SNPs explain 0.43% of the variation in educational attainment (Okbay, 2016).

Woodley & Piffer used a polygenic score using 130 common SNP resulted from the same GWAS (Okbay, 2016). They found a polygenic score of 3,298.5 : (3,298.5 + 3,997.5) = 45.21% for Bronze Age samples and 61666 : (61,666 + 69,114) = 47.15% for today Europeans. We can assume that for only 74 SNP Woodley & Piffer could find the same values of polygenic scores of today Europeans (47.15%) and Bronze Age Eurasians (45.21%). It means an average difference (47.15 – 45.21)% x 74 = 1.44 more IQ-increasing SNP in each today sample, equating with 1.44 x 0.076 = 0.11 IQ points.

Jointly, the variance explained by the 74 SNP is 0.43%, but the variance explained by all the common SNP is 15.6% (Hill, 2017). We can assume that polygenic score increased with (47.15% – 45.21%) = 1.94% for all IQ-increasing common SNP of entire genome. In this case, the average total increase of the genotypic IQ due of common SNP since Bronze Age is (15.6% : 0.43%) x 0.11 IQ points = 3.99 IQ points.

It means the selection pressure on intelligence was strong enough to increase the frequency of common SNP that favor high-IQ with the  the equivalent of 3.99 IQ points.

But common SNP account for 15.6 : (15.6 + 28.1) = 35.67% and rare variants account for 64.33% of genotypic IQ (Hill, 2017). It means the same selection pressure that increased the IQ with 3.99 points on common polymorphism SNP will increase the IQ on rare variants with (64.33% : 35.67%) x 3.99 IQ points = 7.20 IQ points. The total increase of the genotypic IQ will be 3.99 + 7.20 = 11.19 IQ points. In fact, since Bronze Age, the selection eliminated IQ-decreasing common SNP and IQ-decreasing rare variants that equate with 11.19 IQ points.

The average age of Bronze Age samples is 3,440 years, equating with 3,440 : 30 = 114.66 generations. Hence, the selection eliminated IQ-decreasing (common and rare) variants of 11.16 : 114.66 = 0.098 IQ points by generation.

If the average decrease of genotypic intelligence by de novo mutations is higher than 0.098 IQ points by generation, the genotypic IQ of Europeans decreased since Bronze Age.

If we estimate a decrease of 8 IQ points of the genotypic intelligence, due of dysgenic fertility after the demographic transition (started 8 generations ago), the selection could eliminate IQ-decreasing (common and rare) variants (11.6 + 8) : (114.66 – 8) = 0.184 IQ points by generation before the demographic transition. If the average decrease of genotypic IQ by de novo mutations was higher than 0.184 IQ points by generation, the genotypic intelligence of Europeans decreased even before the demographic transition.

PS. The polygenic scores for 9 SNP and 11 SNP are 5% higher for today Europeans than for Bronze Age Europeans. If we assume that for all IQ-increasing common SNP the increase is of 5%, the selection eliminated IQ-decreasing (common and rare) variants equating with (5% : 1.94%) x 0.098 = 0.253 IQ points by generation since Bronze Age, and equating with (5% : 1.94%) x 0.184 = 0.474 IQ points by generation (before Industrial Revolution).

PPS. (26.05.2017) Prevalence of ADHD is 7%. Heritability of ADHD is 75%, hence sporadic cases are 85% of all cases. 36% of sporadic cases of ADHD are due of de novo mutations (Kim, 2017). Paternal age higher than 45 years increases 13 fold the risk for ADHD (D’Onofrio, 2014). The prevalence of ADHD due of de novo mutations is 0.07 x 0.85 x 0.36 = 0.0214

A meta-analysis (Frazier, 2004) found 7 at 11 points lower than average IQ of those with ADHD. In all psychiatric diseases, cases due of de novo mutations have the lowest IQ. We can consider those with ADHD by de novo mutations have at least 11 points lower IQ than average.
The generational lost of genotypic intelligence due of ADHD by de novo mutations is 0.0215 x 11 = 0.236 IQ points.
Also, people with ADHD have higher fertility than average (Williams, 2006).
Even only the generational loss of IQ (0.236 points) due of de novo mutations producing ADHD overcompensated the positive selection on intelligence between Bronze Age and Industrial Revolution found by Woodley & Piffer, that had a strength of 0.184 IQ points by generation.


Hill, D.W. et al. (2017) Genomic analysis of family data reveals additional genetic effects on intelligence and personality. bioRxiv
Kong, A. et al. (2017) Selection against variants in the genome associated
with educational attainment. PNAS 114(5): E727-E732. doi: 10.1073/pnas.1612113114.
Okbay, A. et al. (2016). Genome-wide association study identifies 74 loci associated with educational attainment. Nature 533: 539-542.
Woodley, M.A. et al. (2017) Holocene selection for variants associated with cognitive ability: Comparing ancient and modern genomes. bioRxiv

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