Ultra-rare disruptive and damaging mutations influence educational attainment in the general population

Andrea Ganna; Giulio Genovese; Daniel P Howrigan; Andrea Byrnes; Mitja Kurki; Seyedeh M Zekavat; Christopher W Whelan; Mart Kals; Michel G Nivard; Alex Bloemendal; Jonathan M Bloom; Jacqueline I Goldstein; Timothy Poterba; Cotton Seed; Robert E Handsaker; Pradeep Natarajan; Reedik Mägi; Diane Gage; Elise B Robinson; Andres Metspalu; Veikko Salomaa; Jaana Suvisaari; Shaun M Purcell; Pamela Sklar; Sekar Kathiresan; Mark J Daly; Steven A McCarroll; Patrick F Sullivan; Aarno Palotie; Tõnu Esko; Christina Hultman; Benjamin M Neale

doi:10.1038/nn.4404

Ultra-rare disruptive and damaging mutations influence educational attainment in the general population

Nat Neurosci. 2016 Dec;19(12):1563-1565. doi: 10.1038/nn.4404. Epub 2016 Oct 3.

Authors

Andrea Ganna^#^{1

2

3

4}, Giulio Genovese^#^{2

3

5}, Daniel P Howrigan^{1

2

3}, Andrea Byrnes^{1

2

3}, Mitja Kurki^{1

2

3

6}, Seyedeh M Zekavat^{2

7}, Christopher W Whelan^{2

3

5}, Mart Kals^{8

9}, Michel G Nivard¹⁰, Alex Bloemendal^{1

2

3}, Jonathan M Bloom^{1

2

3}, Jacqueline I Goldstein^{1

2

3}, Timothy Poterba^{1

2

3}, Cotton Seed^{1

2

3}, Robert E Handsaker^{2

3

5}, Pradeep Natarajan^{2

7}, Reedik Mägi⁸, Diane Gage³, Elise B Robinson^{1

2

3}, Andres Metspalu⁸, Veikko Salomaa¹¹, Jaana Suvisaari¹¹, Shaun M Purcell^{12

13}, Pamela Sklar^{12

13}, Sekar Kathiresan^{2

7}, Mark J Daly^{1

2

3}, Steven A McCarroll^{2

3

5}, Patrick F Sullivan^{4

14}, Aarno Palotie^{1

3

6}, Tõnu Esko^{2

8}, Christina Hultman⁴, Benjamin M Neale^{1

2

3}

Affiliations

¹ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston 02114, MA, USA.
² Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
³ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁴ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden.
⁵ Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
⁶ Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki FI-00014, Finland.
⁷ Center for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, 02114, USA.
⁸ Estonian Genome Center, University of Tartu, Tartu 51010, Estonia.
⁹ Institute of Mathematics and Statistics, University of Tartu, Tartu 50409, Estonia.
¹⁰ Department of Biological Psychology, VU University Amsterdam, Amsterdam 1081 HV, The Netherlands.
¹¹ Department of Health, THL-National Institute for Health and Welfare, Helsinki FI-00271, Finland.
¹² Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
¹³ Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
¹⁴ Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill, North Carolina 27599-7264, USA.

^# Contributed equally.

PMID: 27694993
PMCID: PMC5127781
DOI: 10.1038/nn.4404

Abstract

Disruptive, damaging ultra-rare variants in highly constrained genes are enriched in individuals with neurodevelopmental disorders. In the general population, this class of variants was associated with a decrease in years of education (YOE). This effect was stronger among highly brain-expressed genes and explained more YOE variance than pathogenic copy number variation but less than common variants. Disruptive, damaging ultra-rare variants in highly constrained genes influence the determinants of YOE in the general population.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

DNA Copy Number Variations / genetics*
Education
Genetic Predisposition to Disease*
Humans
Mutation / genetics*
Neurodevelopmental Disorders / genetics*
Task Performance and Analysis

Abstract

Publication types

MeSH terms

Grants and funding