Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
30038396
TITLE
Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.
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.
DATE PUBLISHED
2018 07 23
HISTORY
PUBSTATUS PUBSTATUSDATE
retracted 2018/08/01
received 2017/11/06
accepted 2018/04/30
pubmed 2018/07/25 06:00
medline 2019/04/25 06:00
entrez 2018/07/25 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Lee JJ Lee James J JJ Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Wedow R Wedow Robbee R Institute of Behavioral Science, University of Colorado Boulder, Boulder, CO, USA.
Okbay A Okbay Aysu A Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. a.okbay@vu.nl.
Kong E Kong Edward E Department of Economics, Harvard University, Cambridge, MA, USA.
Maghzian O Maghzian Omeed O Department of Economics, Harvard University, Cambridge, MA, USA.
Zacher M Zacher Meghan M Department of Sociology, Harvard University, Cambridge, MA, USA.
Nguyen-Viet TA Nguyen-Viet Tuan Anh TA Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA.
Bowers P Bowers Peter P Department of Economics, Harvard University, Cambridge, MA, USA.
Sidorenko J Sidorenko Julia J Estonian Genome Center, University of Tartu, Tartu, Estonia.
Karlsson Linnér R Karlsson Linnér Richard R Institute for Behavior and Biology, Erasmus University Rotterdam, Rotterdam, The Netherlands.
Fontana MA Fontana Mark Alan MA Center for the Advancement of Value in Musculoskeletal Care, Hospital for Special Surgery, New York, NY, USA.
Kundu T Kundu Tushar T Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA.
Lee C Lee Chanwook C Department of Economics, Harvard University, Cambridge, MA, USA.
Li H Li Hui H Department of Economics, Harvard University, Cambridge, MA, USA.
Li R Li Ruoxi R Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA.
Royer R Royer Rebecca R Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA.
Timshel PN Timshel Pascal N PN Statens Serum Institut, Department of Epidemiology Research, Copenhagen, Denmark.
Walters RK Walters Raymond K RK Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Willoughby EA Willoughby Emily A EA Department of Psychology, University of Minnesota Twin Cities, Minneapolis, MN, USA.
Yengo L Yengo Loïc L Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
23andMe Research Team
COGENT (Cognitive Genomics Consortium)
Social Science Genetic Association Consortium
Alver M Alver Maris M Estonian Genome Center, University of Tartu, Tartu, Estonia.
Bao Y Bao Yanchun Y Institute for Social and Economic Research, University of Essex, Colchester, UK.
Clark DW Clark David W DW Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
Day FR Day Felix R FR MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Furlotte NA Furlotte Nicholas A NA 23andMe, Inc., Mountain View, CA, USA.
Joshi PK Joshi Peter K PK Institute of Social and Preventive Medicine, University Hospital of Lausanne, Lausanne, Switzerland.
Kemper KE Kemper Kathryn E KE Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
Kleinman A Kleinman Aaron A 23andMe, Inc., Mountain View, CA, USA.
Langenberg C Langenberg Claudia C MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Mägi R Mägi Reedik R Estonian Genome Center, University of Tartu, Tartu, Estonia.
Trampush JW Trampush Joey W JW Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Verma SS Verma Shefali Setia SS Department of Biomedical and Translational Informatics, Geisinger Health System, Danville, PA, USA.
Wu Y Wu Yang Y Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
Lam M Lam Max M Genome Institute, Singapore, Singapore.
Zhao JH Zhao Jing Hua JH MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Zheng Z Zheng Zhili Z The Eye Hospital, School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, China.
Boardman JD Boardman Jason D JD Institute of Behavioral Science, University of Colorado Boulder, Boulder, CO, USA.
Campbell H Campbell Harry H Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
Freese J Freese Jeremy J Department of Sociology, Stanford University, Stanford, CA, USA.
Harris KM Harris Kathleen Mullan KM Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Hayward C Hayward Caroline C MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Herd P Herd Pamela P La Follette School of Public Affairs, University of Wisconsin-Madison, Madison, WI, USA.
Kumari M Kumari Meena M Institute for Social and Economic Research, University of Essex, Colchester, UK.
Lencz T Lencz Todd T Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, CA, USA.
Luan J Luan Jian'an J MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Malhotra AK Malhotra Anil K AK Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, CA, USA.
Metspalu A Metspalu Andres A Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Milani L Milani Lili L Estonian Genome Center, University of Tartu, Tartu, Estonia.
Ong KK Ong Ken K KK MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Perry JRB Perry John R B JRB MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Porteous DJ Porteous David J DJ Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Ritchie MD Ritchie Marylyn D MD Department of Biomedical and Translational Informatics, Geisinger Health System, Danville, PA, USA.
Smart MC Smart Melissa C MC Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
Smith BH Smith Blair H BH Medical Research Institute, University of Dundee, Dundee, UK.
Tung JY Tung Joyce Y JY 23andMe, Inc., Mountain View, CA, USA.
Wareham NJ Wareham Nicholas J NJ MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
Wilson JF Wilson James F JF MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Beauchamp JP Beauchamp Jonathan P JP Department of Economics, University of Toronto, Toronto, Ontario, Canada.
Conley DC Conley Dalton C DC Department of Sociology, Princeton University, Princeton, NJ, USA.
Esko T Esko Tõnu T Estonian Genome Center, University of Tartu, Tartu, Estonia.
Lehrer SF Lehrer Steven F SF National Bureau of Economic Research, Cambridge, MA, USA.
Magnusson PKE Magnusson Patrik K E PKE Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Oskarsson S Oskarsson Sven S Department of Government, Uppsala University, Uppsala, Sweden.
Pers TH Pers Tune H TH Statens Serum Institut, Department of Epidemiology Research, Copenhagen, Denmark.
Robinson MR Robinson Matthew R MR Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
Thom K Thom Kevin K Department of Economics, New York University, New York, NY, USA.
Watson C Watson Chelsea C Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA.
Chabris CF Chabris Christopher F CF Autism and Developmental Medicine Institute, Geisinger Health System, Lewisburg, PA, USA.
Meyer MN Meyer Michelle N MN Center for Translational Bioethics and Health Care Policy, Geisinger Health System, Danville, PA, USA.
Laibson DI Laibson David I DI Department of Economics, Harvard University, Cambridge, MA, USA.
Yang J Yang Jian J Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
Johannesson M Johannesson Magnus M Department of Economics, Stockholm School of Economics, Stockholm, Sweden.
Koellinger PD Koellinger Philipp D PD Institute for Behavior and Biology, Erasmus University Rotterdam, Rotterdam, The Netherlands.
Turley P Turley Patrick P Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Visscher PM Visscher Peter M PM Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. peter.visscher@uq.edu.au.
Benjamin DJ Benjamin Daniel J DJ Department of Economics, University of Southern California, Los Angeles, CA, USA. daniel.benjamin@gmail.com.
Cesarini D Cesarini David D Center for Experimental Social Science, New York University, New York, NY, USA.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Agee Michelle M
Alipanahi Babak B
Auton Adam A
Bell Robert K RK
Bryc Katarzyna K
Elson Sarah L SL
Fontanillas Pierre P
Hinds David A DA
McCreight Jennifer C JC
Huber Karen E KE
Litterman Nadia K NK
McIntyre Matthew H MH
Mountain Joanna L JL
Noblin Elizabeth S ES
Northover Carrie A M CAM
Pitts Steven J SJ
Sathirapongsasuti J Fah JF
Sazonova Olga V OV
Shelton Janie F JF
Shringarpure Suyash S
Tian Chao C
Vacic Vladimir V
Wilson Catherine H CH
Okbay Aysu A
Beauchamp Jonathan P JP
Fontana Mark Alan MA
Lee James J JJ
Pers Tune H TH
Rietveld Cornelius A CA
Turley Patrick P
Chen Guo-Bo GB
Emilsson Valur V
Meddens S Fleur W SFW
Oskarsson Sven S
Pickrell Joseph K JK
Thom Kevin K
Timshel Pascal P
Vlaming Ronald de R
Abdellaoui Abdel A
Ahluwalia Tarunveer S TS
Bacelis Jonas J
Baumbach Clemens C
Bjornsdottir Gyda G
Brandsma Johannes H JH
Concas Maria Pina MP
Derringer Jaime J
Furlotte Nicholas A NA
Galesloot Tessel E TE
Girotto Giorgia G
Gupta Richa R
Hall Leanne M LM
Harris Sarah E SE
Hofer Edith E
Horikoshi Momoko M
Huffman Jennifer E JE
Kaasik Kadri K
Kalafati Ioanna P IP
Karlsson Robert R
Kong Augustine A
Lahti Jari J
van der Lee Sven J SJ
Leeuw Christiaan de C
Lind Penelope A PA
Lindgren Karl-Oskar KO
Liu Tian T
Mangino Massimo M
Marten Jonathan J
Mihailov Evelin E
Miller Michael B MB
van der Most Peter J PJ
Oldmeadow Christopher C
Payton Antony A
Pervjakova Natalia N
Peyrot Wouter J WJ
Qian Yong Y
Raitakari Olli O
Rueedi Rico R
Salvi Erika E
Schmidt Börge B
Schraut Katharina E KE
Shi Jianxin J
Smith Albert V AV
Poot Raymond A RA
St Pourcain Beate B
Teumer Alexander A
Thorleifsson Gudmar G
Verweij Niek N
Vuckovic Dragana D
Wellmann Juergen J
Westra Harm-Jan HJ
Yang Jingyun J
Zhao Wei W
Zhu Zhihong Z
Alizadeh Behrooz Z BZ
Amin Najaf N
Bakshi Andrew A
Baumeister Sebastian E SE
Biino Ginevra G
Bønnelykke Klaus K
Boyle Patricia A PA
Campbell Harry H
Cappuccio Francesco P FP
Davies Gail G
De Neve Jan-Emmanuel JE
Deloukas Panos P
Demuth Ilja I
Ding Jun J
Eibich Peter P
Eisele Lewin L
Eklund Niina N
Evans David M DM
Faul Jessica D JD
Feitosa Mary F MF
Forstner Andreas J AJ
Gandin Ilaria I
Gunnarsson Bjarni B
Halldórsson Bjarni V BV
Harris Tamara B TB
Heath Andrew C AC
Hocking Lynne J LJ
Holliday Elizabeth G EG
Homuth Georg G
Horan Michael A MA
Hottenga Jouke-Jan JJ
de Jager Philip L PL
Joshi Peter K PK
Jugessur Astanand A
Kaakinen Marika A MA
Kähönen Mika M
Kanoni Stavroula S
Keltigangas-Järvinen Liisa L
Kiemeney Lambertus A L M LALM
Kolcic Ivana I
Koskinen Seppo S
Kraja Aldi T AT
Kroh Martin M
Kutalik Zoltan Z
Latvala Antti A
Launer Lenore J LJ
Lebreton Maël P MP
Levinson Douglas F DF
Lichtenstein Paul P
Lichtner Peter P
Liewald David C M DCM
Loukola LifeLines Cohort Study Anu LCSA
Madden Pamela A PA
Mägi Reedik R
Mäki-Opas Tomi T
Marioni Riccardo E RE
Marques-Vidal Pedro P
Meddens Gerardus A GA
McMahon George G
Meisinger Christa C
Meitinger Thomas T
Milaneschi Yusplitri Y
Milani Lili L
Montgomery Grant W GW
Myhre Ronny R
Nelson Christopher P CP
Nyholt Dale R DR
Ollier William E R WER
Palotie Aarno A
Paternoster Lavinia L
Pedersen Nancy L NL
Petrovic Katja E KE
Porteous David J DJ
Räikkönen Katri K
Ring Susan M SM
Robino Antonietta A
Rostapshova Olga O
Rudan Igor I
Rustichini Aldo A
Salomaa Veikko V
Sanders Alan R AR
Sarin Antti-Pekka AP
Schmidt Helena H
Scott Rodney J RJ
Smith Blair H BH
Smith Jennifer A JA
Staessen Jan A JA
Steinhagen-Thiessen Elisabeth E
Strauch Konstantin K
Terracciano Antonio A
Tobin Martin D MD
Ulivi Sheila S
Vaccargiu Simona S
Quaye Lydia L
van Rooij Frank J A FJA
Venturini Cristina C
Vinkhuyzen Anna A E AAE
Völker Uwe U
Völzke Henry H
Vonk Judith M JM
Vozzi Diego D
Waage Johannes J
Ware Erin B EB
Willemsen Gonneke G
Attia John R JR
Bennett David A DA
Berger Klaus K
Bertram Lars L
Bisgaard Hans H
Boomsma Dorret I DI
Borecki Ingrid B IB
Bültmann Ute U
Chabris Christopher F CF
Cucca Francesco F
Cusi Daniele D
Deary Ian J IJ
Dedoussis George V GV
van Duijn Cornelia M CM
Eriksson Johan G JG
Franke Barbara B
Franke Lude L
Gasparini Paolo P
Gejman Pablo V PV
Gieger Christian C
Grabe Hans-Jörgen HJ
Gratten Jacob J
Groenen Patrick J F PJF
Gudnason Vilmundur V
van der Harst Pim P
Hayward Caroline C
Hinds David A DA
Hoffmann Wolfgang W
Hyppönen Elina E
Iacono William G WG
Jacobsson Bo B
Järvelin Marjo-Riitta MR
Jöckel Karl-Heinz KH
Kaprio Jaakko J
Kardia Sharon L R SLR
Lehtimäki Terho T
Lehrer Steven F SF
Magnusson Patrik K E PKE
Martin Nicholas G NG
McGue Matt M
Metspalu Andres A
Pendleton Neil N
Penninx Brenda W J H BWJH
Perola Markus M
Pirastu Nicola N
Pirastu Mario M
Polasek Ozren O
Posthuma Danielle D
Power Christine C
Province Michael A MA
Samani Nilesh J NJ
Schlessinger David D
Schmidt Reinhold R
Sørensen Thorkild I A TIA
Spector Tim D TD
Stefansson Kari K
Thorsteinsdottir Unnur U
Thurik A Roy AR
Timpson Nicholas J NJ
Tiemeier Henning H
Tung Joyce Y JY
Uitterlinden André G AG
Vitart Veronique V
Vollenweider Peter P
Weir David R DR
Wilson James F JF
Wright Alan F AF
Conley Dalton C DC
Krueger Robert F RF
Smith George Davey GD
Hofman Albert A
Laibson David I DI
Medland Sarah E SE
Meyer Michelle N MN
Yang Jian J
Johannesson Magnus M
Visscher Peter M PM
Esko Tõnu T
Koellinger Philipp D PD
Cesarini David D
Benjamin Daniel J DJ
JOURNAL
VOLUME: 50
ISSUE: 8
TITLE: Nature genetics
ISOABBREVIATION: Nat Genet
YEAR: 2018
MONTH: 07
DAY: 23
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
CommentIn Nat Rev Genet. 2018 Oct;19(10):592-593 30093724
GRANTS
GRANTID AGENCY COUNTRY
G1001799 Medical Research Council United Kingdom
MR/N01104X/2 Medical Research Council United Kingdom
R01 HD073342 NICHD NIH HHS United States
L30 MH104879 NIMH NIH HHS United States
MR/K026992/1 Medical Research Council United Kingdom
MC_UU_12015/1 Medical Research Council United Kingdom
P30 AG010161 NIA NIH HHS United States
R01 AG055406 NIA NIH HHS United States
Wellcome Trust United Kingdom
R01 AG015819 NIA NIH HHS United States
647648 European Research Council International
MC_UU_12015/2 Medical Research Council United Kingdom
P2C HD047879 NICHD NIH HHS United States
P2C HD066613 NICHD NIH HHS United States
BB/F019394/1 Biotechnology and Biological Sciences Research Council United Kingdom
P01 AG005842 NIA NIH HHS United States
P2C HD050924 NICHD NIH HHS United States
G0600237 Medical Research Council United Kingdom
G0100594 Medical Research Council United Kingdom
P30 AG012810 NIA NIH HHS United States
R01 AG042568 NIA NIH HHS United States
T32 AG000186 NIA NIH HHS United States
BB/F022441/1 Biotechnology and Biological Sciences Research Council United Kingdom
G0901461 Medical Research Council United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Aged
Aged, 80 and over
Cohort Studies
Educational Status
Female
Genome-Wide Association Study methods
Humans methods
Male methods
Middle Aged methods
Multifactorial Inheritance methods
Phenotype methods
Polymorphism, Single Nucleotide methods
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's