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Investigating the Genetic Architecture of Non-Cognitive Skills Using GWAS-by-Subtraction

View ORCID ProfilePerline A. Demange, View ORCID ProfileMargherita Malanchini, Travis T. Mallard, Pietro Biroli, Simon R. Cox, Andrew D. Grotzinger, Elliot M. Tucker-Drob, Abdel Abdellaoui, Louise Arseneault, Avshalom Caspi, David Corcoran, Benjamin Domingue, Colter Mitchell, Elsje van Bergen, Dorret I. Boomsma, Kathleen M. Harris, Hill F. Ip, Terrie E. Moffitt, Richie Poulton, Joseph Prinz, Karen Sugden, Jasmin Wertz, Benjamin Williams, Eveline L. de Zeeuw, View ORCID ProfileDaniel W. Belsky, K. Paige Harden, View ORCID ProfileMichel G. Nivard
doi: https://doi.org/10.1101/2020.01.14.905794
Perline A. Demange
1Department of Biological Psychology, Vrije Universiteit Amsterdam, The Netherlands
2Amsterdam Public Health Research Institute, Amsterdam University Medical Centers, Amsterdam, The Netherlands
3Research Institute LEARN!,Vrije Universiteit Amsterdam, The Netherlands
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  • ORCID record for Perline A. Demange
Margherita Malanchini
4Department of Biological and Experimental Psychology, Queen Mary University of London, UK
5Social, Genetic and Developmental Psychiatric Centre, Institute of Psychiatry, King’s College London, UK
6Department of Psychology, University of Texas at Austin, USA
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Travis T. Mallard
6Department of Psychology, University of Texas at Austin, USA
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Pietro Biroli
7Department of Economics, University of Zurich, Switzerland
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Simon R. Cox
8Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, UK
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Andrew D. Grotzinger
6Department of Psychology, University of Texas at Austin, USA
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Elliot M. Tucker-Drob
6Department of Psychology, University of Texas at Austin, USA
9Population Research Center, University of Texas at Austin, USA
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Abdel Abdellaoui
1Department of Biological Psychology, Vrije Universiteit Amsterdam, The Netherlands
10Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
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Louise Arseneault
5Social, Genetic and Developmental Psychiatric Centre, Institute of Psychiatry, King’s College London, UK
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Avshalom Caspi
5Social, Genetic and Developmental Psychiatric Centre, Institute of Psychiatry, King’s College London, UK
11Department of Psychology & Neuroscience, Duke University, Durham, NC, USA
12Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA
13Center for Genomic and Computational Biology, Duke University, Durham, NC, USA
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David Corcoran
13Center for Genomic and Computational Biology, Duke University, Durham, NC, USA
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Benjamin Domingue
14Stanford Graduate School of Education, Stanford University, Palo Alto, CA, USA
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Colter Mitchell
15Institute for Social Research, University of Michigan, Ann Arbor, USA
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Elsje van Bergen
1Department of Biological Psychology, Vrije Universiteit Amsterdam, The Netherlands
3Research Institute LEARN!,Vrije Universiteit Amsterdam, The Netherlands
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Dorret I. Boomsma
1Department of Biological Psychology, Vrije Universiteit Amsterdam, The Netherlands
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Kathleen M. Harris
16Carolina Population Center and Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Hill F. Ip
1Department of Biological Psychology, Vrije Universiteit Amsterdam, The Netherlands
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Terrie E. Moffitt
5Social, Genetic and Developmental Psychiatric Centre, Institute of Psychiatry, King’s College London, UK
11Department of Psychology & Neuroscience, Duke University, Durham, NC, USA
12Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA
13Center for Genomic and Computational Biology, Duke University, Durham, NC, USA
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Richie Poulton
17Department of Psychology and Dunedin Multidisciplinary Health and Development Research Unit, University of Otago, Otago, NZ
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Joseph Prinz
13Center for Genomic and Computational Biology, Duke University, Durham, NC, USA
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Karen Sugden
11Department of Psychology & Neuroscience, Duke University, Durham, NC, USA
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Jasmin Wertz
11Department of Psychology & Neuroscience, Duke University, Durham, NC, USA
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Benjamin Williams
11Department of Psychology & Neuroscience, Duke University, Durham, NC, USA
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Eveline L. de Zeeuw
1Department of Biological Psychology, Vrije Universiteit Amsterdam, The Netherlands
3Research Institute LEARN!,Vrije Universiteit Amsterdam, The Netherlands
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Daniel W. Belsky
18Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA
19Robert N. Butler Columbia Aging Center, Columbia University, New York, NY, USA
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K. Paige Harden
6Department of Psychology, University of Texas at Austin, USA
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Michel G. Nivard
1Department of Biological Psychology, Vrije Universiteit Amsterdam, The Netherlands
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  • For correspondence: m.g.nivard@vu.nl
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Abstract

Educational attainment (EA) is influenced by cognitive abilities and by other characteristics and traits. However little is known about the genetic architecture of these “non-cognitive” contributions to EA. Here, we use Genomic Structural Equation Modelling and results of prior genome-wide association studies (GWASs) of EA (N = 1,131,881) and cognitive test performance (N = 257,841) to estimate SNP associations with variation in EA that is independent of cognitive ability. We identified 157 genome-wide significant loci and a polygenic architecture accounting for 57% of genetic variance in EA. Phenotypic and biological annotation revealed that (1) both cognitive and non-cognitive contributions to EA were genetically correlated with socioeconomic success and longevity; and (2) non-cognitive contributions to EA were related to personality, decision making, risk-behavior, and increased risk for psychiatric disorders; (3) non-cognitive and cognitive contributions to EA were enriched in the same tissues and cell types, but (4) showed different associations with gray-matter neuroimaging phenotypes.

Footnotes

  • ↵# Jointly supervised the work

  • “It takes something more than intelligence to act intelligently.” – Fyodor Dostoyevksy, Crime and Punishment

  • https://medium.com/@kph3k/investigating-the-genetic-architecture-of-non-cognitive-skills-using-gwas-by-subtraction-b8743773ce44

  • https://www.dropbox.com/s/cvzcedsfhbznv36/GWAS_sumstats_Cog_NonCog_Demange_et_al.zip?dl=0

  • http://rpubs.com/MichelNivard/565885

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted January 15, 2020.
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Investigating the Genetic Architecture of Non-Cognitive Skills Using GWAS-by-Subtraction
Perline A. Demange, Margherita Malanchini, Travis T. Mallard, Pietro Biroli, Simon R. Cox, Andrew D. Grotzinger, Elliot M. Tucker-Drob, Abdel Abdellaoui, Louise Arseneault, Avshalom Caspi, David Corcoran, Benjamin Domingue, Colter Mitchell, Elsje van Bergen, Dorret I. Boomsma, Kathleen M. Harris, Hill F. Ip, Terrie E. Moffitt, Richie Poulton, Joseph Prinz, Karen Sugden, Jasmin Wertz, Benjamin Williams, Eveline L. de Zeeuw, Daniel W. Belsky, K. Paige Harden, Michel G. Nivard
bioRxiv 2020.01.14.905794; doi: https://doi.org/10.1101/2020.01.14.905794
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Investigating the Genetic Architecture of Non-Cognitive Skills Using GWAS-by-Subtraction
Perline A. Demange, Margherita Malanchini, Travis T. Mallard, Pietro Biroli, Simon R. Cox, Andrew D. Grotzinger, Elliot M. Tucker-Drob, Abdel Abdellaoui, Louise Arseneault, Avshalom Caspi, David Corcoran, Benjamin Domingue, Colter Mitchell, Elsje van Bergen, Dorret I. Boomsma, Kathleen M. Harris, Hill F. Ip, Terrie E. Moffitt, Richie Poulton, Joseph Prinz, Karen Sugden, Jasmin Wertz, Benjamin Williams, Eveline L. de Zeeuw, Daniel W. Belsky, K. Paige Harden, Michel G. Nivard
bioRxiv 2020.01.14.905794; doi: https://doi.org/10.1101/2020.01.14.905794

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