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Research Article

Selection against variants in the genome associated with educational attainment

Augustine Kong, Michael L. Frigge, Gudmar Thorleifsson, Hreinn Stefansson, Alexander I. Young, Florian Zink, Gudrun A. Jonsdottir, View ORCID ProfileAysu Okbay, Patrick Sulem, Gisli Masson, Daniel F. Gudbjartsson, Agnar Helgason, Gyda Bjornsdottir, Unnur Thorsteinsdottir, and Kari Stefansson
PNAS January 31, 2017 114 (5) E727-E732; first published January 17, 2017; https://doi.org/10.1073/pnas.1612113114
Augustine Kong
adeCODE genetics/Amgen Inc., Reykjavik 101, Iceland;
bSchool of Engineering and Natural Sciences, University of Iceland, Reykjavik 101, Iceland;
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  • For correspondence: kong@decode.is kari.stefansson@decode.is
Michael L. Frigge
adeCODE genetics/Amgen Inc., Reykjavik 101, Iceland;
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Gudmar Thorleifsson
adeCODE genetics/Amgen Inc., Reykjavik 101, Iceland;
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Hreinn Stefansson
adeCODE genetics/Amgen Inc., Reykjavik 101, Iceland;
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Alexander I. Young
cWellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, United Kingdom;
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Florian Zink
adeCODE genetics/Amgen Inc., Reykjavik 101, Iceland;
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Gudrun A. Jonsdottir
adeCODE genetics/Amgen Inc., Reykjavik 101, Iceland;
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Aysu Okbay
dDepartment of Applied Economics, Erasmus School of Applied Economics, Erasmus University Rotterdam, 3062 PA Rotterdam, The Netherlands;
eInstitute for Behavior and Biology, Erasmus University Rotterdam, 3062 PA Rotterdam, The Netherlands;
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  • ORCID record for Aysu Okbay
Patrick Sulem
adeCODE genetics/Amgen Inc., Reykjavik 101, Iceland;
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Gisli Masson
adeCODE genetics/Amgen Inc., Reykjavik 101, Iceland;
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Daniel F. Gudbjartsson
adeCODE genetics/Amgen Inc., Reykjavik 101, Iceland;
bSchool of Engineering and Natural Sciences, University of Iceland, Reykjavik 101, Iceland;
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Agnar Helgason
adeCODE genetics/Amgen Inc., Reykjavik 101, Iceland;
fDepartment of Anthropology, University of Iceland, Reykjavik 101, Iceland;
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Gyda Bjornsdottir
adeCODE genetics/Amgen Inc., Reykjavik 101, Iceland;
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Unnur Thorsteinsdottir
adeCODE genetics/Amgen Inc., Reykjavik 101, Iceland;
gFaculty of Medicine, University of Iceland, Reykjavik 101, Iceland
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Kari Stefansson
adeCODE genetics/Amgen Inc., Reykjavik 101, Iceland;
gFaculty of Medicine, University of Iceland, Reykjavik 101, Iceland
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  • For correspondence: kong@decode.is kari.stefansson@decode.is
  1. Edited by Andrew G. Clark, Cornell University, Ithaca, NY, and approved December 5, 2016 (received for review July 22, 2016)

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Significance

Epidemiological studies suggest that educational attainment is affected by genetic variants. Results from recent genetic studies allow us to construct a score from a person’s genotypes that captures a portion of this genetic component. Using data from Iceland that include a substantial fraction of the population we show that individuals with high scores tend to have fewer children, mainly because they have children later in life. Consequently, the average score has been decreasing over time in the population. The rate of decrease is small per generation but marked on an evolutionary timescale. Another important observation is that the association between the score and fertility remains highly significant after adjusting for the educational attainment of the individuals.

Abstract

Epidemiological and genetic association studies show that genetics play an important role in the attainment of education. Here, we investigate the effect of this genetic component on the reproductive history of 109,120 Icelanders and the consequent impact on the gene pool over time. We show that an educational attainment polygenic score, POLYEDU, constructed from results of a recent study is associated with delayed reproduction (P < 10−100) and fewer children overall. The effect is stronger for women and remains highly significant after adjusting for educational attainment. Based on 129,808 Icelanders born between 1910 and 1990, we find that the average POLYEDU has been declining at a rate of ∼0.010 standard units per decade, which is substantial on an evolutionary timescale. Most importantly, because POLYEDU only captures a fraction of the overall underlying genetic component the latter could be declining at a rate that is two to three times faster.

  • selection
  • educational attainment
  • genes
  • fertility
  • sequence variants

Footnotes

  • ↵1To whom correspondence may be addressed. Email: kong{at}decode.is or kari.stefansson{at}decode.is.
  • Author contributions: A.K. and K.S. designed research; A.K., H.S., A.I.Y., G.A.J., A.O., P.S., G.M., D.F.G., A.H., G.B., and U.T. performed research; A.K., M.L.F., G.T., and F.Z. analyzed data; A.K. derived the mathematical results in Materials and Methods; M.L.F. prepared the figures and tables for publication; H.S. provided IQ data and references; G.A.J. processed the IQ data to a form suitable for analyses; A.I.Y. assisted in deriving the mathematical results in Materials and Methods; A.O. provided meta-analysis results with various cohorts removed; P.S., G.M., and D.F.G. contributed to processing the Icelandic genotype data for analysis; A.H. provided key references and contributed to writing the Discussion; G.B. collected and processed Icelandic education data and provided key references; U.T. oversaw the generation of the genotype data in the laboratory; A.K. wrote the paper; and K.S. contributed to the writing of the final version of the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1612113114/-/DCSupplemental.

Freely available online through the PNAS open access option.

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Selection of variants associated with education
Augustine Kong, Michael L. Frigge, Gudmar Thorleifsson, Hreinn Stefansson, Alexander I. Young, Florian Zink, Gudrun A. Jonsdottir, Aysu Okbay, Patrick Sulem, Gisli Masson, Daniel F. Gudbjartsson, Agnar Helgason, Gyda Bjornsdottir, Unnur Thorsteinsdottir, Kari Stefansson
Proceedings of the National Academy of Sciences Jan 2017, 114 (5) E727-E732; DOI: 10.1073/pnas.1612113114

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Selection of variants associated with education
Augustine Kong, Michael L. Frigge, Gudmar Thorleifsson, Hreinn Stefansson, Alexander I. Young, Florian Zink, Gudrun A. Jonsdottir, Aysu Okbay, Patrick Sulem, Gisli Masson, Daniel F. Gudbjartsson, Agnar Helgason, Gyda Bjornsdottir, Unnur Thorsteinsdottir, Kari Stefansson
Proceedings of the National Academy of Sciences Jan 2017, 114 (5) E727-E732; DOI: 10.1073/pnas.1612113114
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