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Nat Genet. 2018 Aug;50(8):1112-1121. doi: 10.1038/s41588-018-0147-3. Epub 2018 Jul 23.

Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.

Collaborators (278)

Agee M, Alipanahi B, Auton A, Bell RK, Bryc K, Elson SL, Fontanillas P, Hinds DA, McCreight JC, Huber KE, Litterman NK, McIntyre MH, Mountain JL, Noblin ES, Northover CAM, Pitts SJ, Sathirapongsasuti JF, Sazonova OV, Shelton JF, Shringarpure S, Tian C, Vacic V, Wilson CH, Okbay A, Beauchamp JP, Fontana MA, Lee JJ, Pers TH, Rietveld CA, Turley P, Chen GB, Emilsson V, Meddens SFW, Oskarsson S, Pickrell JK, Thom K, Timshel P, Vlaming R, Abdellaoui A, Ahluwalia TS, Bacelis J, Baumbach C, Bjornsdottir G, Brandsma JH, Concas MP, Derringer J, Furlotte NA, Galesloot TE, Girotto G, Gupta R, Hall LM, Harris SE, Hofer E, Horikoshi M, Huffman JE, Kaasik K, Kalafati IP, Karlsson R, Kong A, Lahti J, van der Lee SJ, Leeuw C, Lind PA, Lindgren KO, Liu T, Mangino M, Marten J, Mihailov E, Miller MB, van der Most PJ, Oldmeadow C, Payton A, Pervjakova N, Peyrot WJ, Qian Y, Raitakari O, Rueedi R, Salvi E, Schmidt B, Schraut KE, Shi J, Smith AV, Poot RA, St Pourcain B, Teumer A, Thorleifsson G, Verweij N, Vuckovic D, Wellmann J, Westra HJ, Yang J, Zhao W, Zhu Z, Alizadeh BZ, Amin N, Bakshi A, Baumeister SE, Biino G, Bønnelykke K, Boyle PA, Campbell H, Cappuccio FP, Davies G, De Neve JE, Deloukas P, Demuth I, Ding J, Eibich P, Eisele L, Eklund N, Evans DM, Faul JD, Feitosa MF, Forstner AJ, Gandin I, Gunnarsson B, Halldórsson BV, Harris TB, Heath AC, Hocking LJ, Holliday EG, Homuth G, Horan MA, Hottenga JJ, de Jager PL, Joshi PK, Jugessur A, Kaakinen MA, Kähönen M, Kanoni S, Keltigangas-Järvinen L, Kiemeney LALM, Kolcic I, Koskinen S, Kraja AT, Kroh M, Kutalik Z, Latvala A, Launer LJ, Lebreton MP, Levinson DF, Lichtenstein P, Lichtner P, Liewald DCM, Loukola LCSA, Madden PA, Mägi R, Mäki-Opas T, Marioni RE, Marques-Vidal P, Meddens GA, McMahon G, Meisinger C, Meitinger T, Milaneschi Y, Milani L, Montgomery GW, Myhre R, Nelson CP, Nyholt DR, Ollier WER, Palotie A, Paternoster L, Pedersen NL, Petrovic KE, Porteous DJ, Räikkönen K, Ring SM, Robino A, Rostapshova O, Rudan I, Rustichini A, Salomaa V, Sanders AR, Sarin AP, Schmidt H, Scott RJ, Smith BH, Smith JA, Staessen JA, Steinhagen-Thiessen E, Strauch K, Terracciano A, Tobin MD, Ulivi S, Vaccargiu S, Quaye L, van Rooij FJA, Venturini C, Vinkhuyzen AAE, Völker U, Völzke H, Vonk JM, Vozzi D, Waage J, Ware EB, Willemsen G, Attia JR, Bennett DA, Berger K, Bertram L, Bisgaard H, Boomsma DI, Borecki IB, Bültmann U, Chabris CF, Cucca F, Cusi D, Deary IJ, Dedoussis GV, van Duijn CM, Eriksson JG, Franke B, Franke L, Gasparini P, Gejman PV, Gieger C, Grabe HJ, Gratten J, Groenen PJF, Gudnason V, van der Harst P, Hayward C, Hinds DA, Hoffmann W, Hyppönen E, Iacono WG, Jacobsson B, Järvelin MR, Jöckel KH, Kaprio J, Kardia SLR, Lehtimäki T, Lehrer SF, Magnusson PKE, Martin NG, McGue M, Metspalu A, Pendleton N, Penninx BWJH, Perola M, Pirastu N, Pirastu M, Polasek O, Posthuma D, Power C, Province MA, Samani NJ, Schlessinger D, Schmidt R, Sørensen TIA, Spector TD, Stefansson K, Thorsteinsdottir U, Thurik AR, Timpson NJ, Tiemeier H, Tung JY, Uitterlinden AG, Vitart V, Vollenweider P, Weir DR, Wilson JF, Wright AF, Conley DC, Krueger RF, Smith GD, Hofman A, Laibson DI, Medland SE, Meyer MN, Yang J, Johannesson M, Visscher PM, Esko T, Koellinger PD, Cesarini D, Benjamin DJ.

Author information

1
Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
2
Department of Sociology, University of Colorado Boulder, Boulder, CO, USA.
3
Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
4
Institute of Behavioral Science, University of Colorado Boulder, Boulder, CO, USA.
5
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. a.okbay@vu.nl.
6
Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. a.okbay@vu.nl.
7
Department of Economics, Harvard University, Cambridge, MA, USA.
8
Department of Sociology, Harvard University, Cambridge, MA, USA.
9
Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA.
10
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
11
Estonian Genome Center, University of Tartu, Tartu, Estonia.
12
Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
13
Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
14
Institute for Behavior and Biology, Erasmus University Rotterdam, Rotterdam, The Netherlands.
15
Center for the Advancement of Value in Musculoskeletal Care, Hospital for Special Surgery, New York, NY, USA.
16
The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark.
17
Statens Serum Institut, Department of Epidemiology Research, Copenhagen, Denmark.
18
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
19
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
20
Institute for Social and Economic Research, University of Essex, Colchester, UK.
21
Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
22
MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
23
23andMe, Inc., Mountain View, CA, USA.
24
Institute of Social and Preventive Medicine, University Hospital of Lausanne, Lausanne, Switzerland.
25
BrainWorkup, LLC, Santa Monica, CA, USA.
26
Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
27
Department of Biomedical and Translational Informatics, Geisinger Health System, Danville, PA, USA.
28
Institute of Mental Health, Singapore, Singapore.
29
Genome Institute, Singapore, Singapore.
30
The Eye Hospital, School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, China.
31
Department of Sociology, Stanford University, Stanford, CA, USA.
32
Department of Sociology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
33
Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
34
MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
35
La Follette School of Public Affairs, University of Wisconsin-Madison, Madison, WI, USA.
36
Departments of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA.
37
Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA.
38
Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, CA, USA.
39
Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
40
Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
41
Division of Population Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK.
42
Medical Research Institute, University of Dundee, Dundee, UK.
43
Department of Economics, University of Toronto, Toronto, Ontario, Canada.
44
Department of Sociology, Princeton University, Princeton, NJ, USA.
45
School of Policy Studies, Queen's University, Kingston, Ontario, Canada.
46
Department of Economics, New York University Shanghai, Pudong, Shanghai, China.
47
National Bureau of Economic Research, Cambridge, MA, USA.
48
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
49
Department of Government, Uppsala University, Uppsala, Sweden.
50
Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
51
Department of Economics, New York University, New York, NY, USA.
52
Autism and Developmental Medicine Institute, Geisinger Health System, Lewisburg, PA, USA.
53
Center for Translational Bioethics and Health Care Policy, Geisinger Health System, Danville, PA, USA.
54
Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
55
Department of Economics, Stockholm School of Economics, Stockholm, Sweden.
56
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. peter.visscher@uq.edu.au.
57
Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. peter.visscher@uq.edu.au.
58
Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA. daniel.benjamin@gmail.com.
59
National Bureau of Economic Research, Cambridge, MA, USA. daniel.benjamin@gmail.com.
60
Department of Economics, University of Southern California, Los Angeles, CA, USA. daniel.benjamin@gmail.com.
61
Center for Experimental Social Science, New York University, New York, NY, USA.

Abstract

Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.

PMID:
30038396
DOI:
10.1038/s41588-018-0147-3

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