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ARE PSYCHIATRIC DISORDERS THE RESULT OF POSITIVE SELECTION OF VARIANTS THAT FAVOR SELF-DOMESTICATION?

August 18, 2017

A very recent large-scale cognitive GWAS meta-analysis (Lam, 2017) found 70 independent genomic loci associated with intelligence. Even more exciting, this meta-analysis found that only half of the EDU-increasing SNP found by the largest GWAS on EDU (Okbay, 2016) are IQ-increasing variants. Probably the other half of the EDU-increasing SNP are (self-)domestication-increasing variants. Perhaps these variants were under strong positive selection especially after the entrance in Neolithic and in Complex Civilization of populations. It could explain why Piffer (2016) found the lowest POLY_EDU in Africans and Amerindians, the last populations that entered in Neolithic and complex civilization. Also, if two populations have the same POLY_EDU, it is expected that the population that firstly started agriculture has more variants associated with self-domestication, and fewer variants associated with intelligence. Also, the higher POLY_EDU of today Europeans than Bronze Age Europeans, found by Woodley & Piffer (2017), could be explained by the increase of frequency of variants associated with self-domestication, and not by the raise of frequency of IQ-increasing variants.

Another very recent study (Davies, 2017) found 99 genomic loci associated with intelligence. Also, this study found important negative genetic correlations between intelligence and psychiatric disorders: Alzheimer’s disease (-0.38), ADHD (-0.36), major depressive disorder (-0.30), schizophrenia (-0.25), neuroticism (-0.16), bipolar disorder (-0.09). These correlations are stronger that correlations found by the GWAS on IQ of Sniekers (2017), that found also negative genetic correlations of intelligence with depressive symptoms (-0.27), anxiety (-0.19) and insomnia (-0.14). Furthermore, a recent study (Mullins, 2017) found a positive correlation between fertility and POLY_ADHD (0.15) and POLY_MDD (0.04) in today healthy Icelanders, that is in line with selection against high IQ in today Europeans. Also, Mullins (2017) found a negative correlation between fertility and POLY_ASD (-0.25) even in healthy individuals, but ASD is the only psychiatric disorder that is positively correlated with intelligence at genetic level.

Probably the selection on intelligence was associated with selection on neuropsychiatric disorders in the past too. A very interesting recent paper (Berens, 2017) evaluated the genotypic health of ancient humans by polygenic risk scores for diseases. All ancient populations had lower risk scores than today humans for neuropsychiatric diseases. It means there were not selection against the genetic risk of mental disorders or even this polygenic risk was positively selected. It is possible a high polygenic risk for neuropsychiatric disorders favored the self-domestication of humans, because the domestication is, in fact, a disease of the neural crest (Wilkins, 2014). The GWAS on EDU of Okbay (2016) found positive genetic correlations between educational attainment and bipolar disorder (0.28) and schizophrenia (0.10), despite the negative correlations of both diseases with intelligence.  Furthermore, polygenic scores for schizophrenia and educational attainment are associated with behavioural problems in early childhood in the general population (Jansen, 2017). Benitez-Burraco (2017) demonstrated that people with schizophrenia exhibit more marked domesticated traits at the morphological, physiological, and behavioral levels. Also, he found that genes involved in domestication and neural crest development and function comprise nearly 20% of schizophrenia candidates, most of which exhibit altered expression profiles in the brain of patients, specifically in areas involved in language processing.

If the selection on intelligence was (negatively) associated with selection on mental disorders during last thousands of years, and if POLY_PSY increased since Palaeolithic period, I expect POLY_IQ did not significantly increase or even decreased during the same period. Although, the frequency of 122 SNP that favor schizophrenia predicts better the measured IQ of superpopulations in 1000 GENOMES (Cretan, 2017) than the frequency of 15 lead SNP found by the GWAS of Sniekers (Piffer, 2017).

 

REFERENCES

 

Benitez-Burraco, A. (2017) Schizophrenia and Human Self-Domestication: An Evolutionary Linguistic Approach. Brain Behav Evol. 89(3):162-184. doi: 10.1159/000468506.

 

Berens, A.J. et al. (2017) The genomic health of ancient hominins. bioRxiv doi: http://dx.doi.org/10.1101/145193 .

 

Cretan, C. (2017) https://constantincretan.wordpress.com/2017/07/22/new-evidence-for-the-decrease-of-genotypic-intelligence-since-the-palaeolithic-period/

 

Davies, G. et al. (2017) Ninety-nine independent genetic loci influencing general cognitive function include genes
associated with brain health and structure (N = 280,360). bioRxiv doi: http://dx.doi.org/10.1101/176511 .

 

Jansen, P.R. et al. (2017) Polygenic scores for schizophrenia and educational attainment are associated with behavioural problems in early childhood in the general population. The Journal of Child Psychology and Psychiatry DOI: 10.1111/jcpp.12759

 

Lam, M. et al. (2017) Large-scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets. bioRxiv doi: http://dx.doi.org/10.1101/176842 .

 

Mullins, N. et al. (2017) Reproductive fitness and genetic risk of psychiatric
disorders in the general population. NATURE COMMUNICATIONS | 8:15833 | DOI: 10.1038/ncomms15833.

 

Okbay, A. et al. (2016). Genome-wide association study identifies 74 loci associated with educational attainment. Nature 533: 539-542.

 

Piffer, D. (2016). Polygenic selection on educational attainment: a replication. https://figshare.com/article/Polygenic_selection_on_educational_attainment_a_replication/3381439

 

Piffer, D. (2017)  2017 Intelligence GWAS: Group-level polygenic scores http://rpubs.com/Daxide/279148

 

Sniekers, S. et al (2017) Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence. Nature Genetics doi:10.1038/ng.3869

 

Wilkins, A.S. et al. (2014) The “Domestication Syndrome” in Mammals: A Unified Explanation Based on Neural Crest Cell Behavior and Genetics. 

 

Woodley, M.A. et al. (2017) Holocene selection for variants associated with cognitive ability: Comparing ancient and modern genomes. bioRxiv http://dx.doi.org/10.1101/109678

 

 

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