Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

23andMe Research team; Social Science Genetic Association Consortium; Lifelines Cohort Study

doi:10.1038/s41588-022-01016-z

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

23andMe Research team, Social Science Genetic Association Consortium, Lifelines Cohort Study

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12–16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI’s magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.

Original language	English
Pages (from-to)	437-449
Number of pages	13
Journal	Nature Genetics
Volume	54
Issue number	4
DOIs	https://doi.org/10.1038/s41588-022-01016-z
Publication status	Published - 1 Apr 2022

Access to Document

10.1038/s41588-022-01016-z

Cite this

@article{5810d89b49c142e9a4db799cbe79e584,

title = "Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals",

abstract = "We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12–16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI{\textquoteright}s magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.",

author = "Aysu Okbay and Yeda Wu and Nancy Wang and Hariharan Jayashankar and Michael Bennett and Nehzati, {Seyed Moeen} and Julia Sidorenko and Hyeokmoon Kweon and Grant Goldman and Tamara Gjorgjieva and Yunxuan Jiang and Barry Hicks and Chao Tian and Hinds, {David A.} and Rafael Ahlskog and Magnusson, {Patrik K. E.} and Sven Oskarsson and Caroline Hayward and Archie Campbell and Porteous, {David J.} and Jeremy Freese and Pamela Herd and Michelle Agee and Babak Alipanahi and Adam Auton and Bell, {Robert K.} and Katarzyna Bryc and Elson, {Sarah L.} and Pierre Fontanillas and Furlotte, {Nicholas A.} and Hinds, {David A.} and Huber, {Karen E.} and Aaron Kleinman and Litterman, {Nadia K.} and McCreight, {Jennifer C.} and McIntyre, {Matthew H.} and Mountain, {Joanna L.} and Northover, {Carrie A. M.} and Pitts, {Steven J.} and Sathirapongsasuti, {J. Fah} and Sazonova, {Olga V.} and Shelton, {Janie F.} and Suyash Shringarpure and Tung, {Joyce Y.} and Vladimir Vacic and Wilson, {Catherine H.} and Fontana, {Mark Alan} and Pers, {Tune H.} and Rietveld, {Cornelius A.} and Guo-Bo Chen and Valur Emilsson and Meddens, {S. Fleur W.} and Pickrell, {Joseph K.} and Kevin Thom and Pascal Timshel and {de Vlaming}, Ronald and Abdel Abdellaoui and Ahluwalia, {Tarunveer S.} and Jonas Bacelis and Clemens Baumbach and Gyda Bjornsdottir and Brandsma, {Johannes H.} and Concas, {Maria Pina} and Jaime Derringer and Galesloot, {Tessel E.} and Giorgia Girotto and Richa Gupta and Hall, {Leanne M.} and Harris, {Sarah E.} and Edith Hofer and Momoko Horikoshi and Huffman, {Jennifer E.} and Kadri Kaasik and Kalafati, {Ioanna P.} and Robert Karlsson and Jari Lahti and {van der Lee}, {Sven J.} and {de Leeuw}, Christiaan and Lind, {Penelope A.} and Karl-Oskar Lindgren and Tian Liu and Massimo Mangino and Jonathan Marten and Evelin Mihailov and Miller, {Michael B.} and {van der Most}, {Peter J.} and Christopher Oldmeadow and Antony Payton and Natalia Pervjakova and Peyrot, {Wouter J.} and Yong Qian and Olli Raitakari and Rico Rueedi and Erika Salvi and Schmidt, {B. rge} and Schraut, {Katharina E.} and Jianxin Shi and Smith, {Albert V.} and Poot, {Raymond A.} and Pourcain, {Beate St} and Alexander Teumer and Gudmar Thorleifsson and Niek Verweij and Dragana Vuckovic and Juergen Wellmann and Harm-Jan Westra and Jingyun Yang and Wei Zhao and Zhihong Zhu and Alizadeh, {Behrooz Z.} and Najaf Amin and Andrew Bakshi and Baumeister, {Sebastian E.} and Ginevra Biino and Klaus B{\o}nnelykke and Boyle, {Patricia A.} and Harry Campbell and Cappuccio, {Francesco P.} and Gail Davies and {de Neve}, Jan-Emmanuel and Panos Deloukas and Ilja Demuth and Jun Ding and Peter Eibich and Lewin Eisele and Niina Eklund and Evans, {David M.} and Faul, {Jessica D.} and Feitosa, {Mary F.} and Forstner, {Andreas J.} and Ilaria Gandin and Bjarni Gunnarsson and Halld{\'o}rsson, {Bjarni V.} and Harris, {Tamara B.} and Heath, {Andrew C.} and Hocking, {Lynne J.} and Holliday, {Elizabeth G.} and Georg Homuth and Horan, {Michael A.} and Jouke-Jan Hottenga and {de Jager}, {Philip L.} and Joshi, {Peter K.} and Astanand Jugessur and Kaakinen, {Marika A.} and Mika K{\"a}h{\"o}nen and Stavroula Kanoni and Liisa Keltigangas-J{\"a}rvinen and Kiemeney, {Lambertus A. L. M.} and Ivana Kolcic and Seppo Koskinen and Kraja, {Aldi T.} and Martin Kroh and Zoltan Kutalik and Antti Latvala and Launer, {Lenore J.} and Lebreton, {Ma{\"e}l P.} and Levinson, {Douglas F.} and Paul Lichtenstein and Peter Lichtner and Liewald, {David C. M.} and Anu Loukola and Madden, {Pamela A.} and Reedik M{\"a}gi and Tomi M{\"a}ki-Opas and Marioni, {Riccardo E.} and Pedro Marques-Vidal and Meddens, {Gerardus A.} and George McMahon and Christa Meisinger and Thomas Meitinger and Yusplitri Milaneschi and Lili Milani and Montgomery, {Grant W.} and Ronny Myhre and Nelson, {Christopher P.} and Nyholt, {Dale R.} and Ollier, {William E. R.} and Aarno Palotie and Lavinia Paternoster and Pedersen, {Nancy L.} and Petrovic, {Katja E.} and Katri R{\"a}ikk{\"o}nen and Ring, {Susan M.} and Antonietta Robino and Olga Rostapshova and Igor Rudan and Aldo Rustichini and Veikko Salomaa and Sanders, {Alan R.} and Antti-Pekka Sarin and Helena Schmidt and Scott, {Rodney J.} and Smith, {Blair H.} and Smith, {Jennifer A.} and Staessen, {Jan A.} and Elisabeth Steinhagen-Thiessen and Konstantin Strauch and Antonio Terracciano and Tobin, {Martin D.} and Sheila Ulivi and Simona Vaccargiu and Lydia Quaye and {van Rooij}, {Frank J. A.} and Cristina Venturini and Vinkhuyzen, {Anna A. E.} and Uwe V{\"o}lker and Henry V{\"o}lzke and Vonk, {Judith M.} and Diego Vozzi and Johannes Waage and Ware, {Erin B.} and Gonneke Willemsen and Attia, {John R.} and Bennett, {David A.} and Klaus Berger and Lars Bertram and Hans Bisgaard and Boomsma, {Dorret I.} and Borecki, {Ingrid B.} and Ute B{\"u}ltmann and Chabris, {Christopher F.} and Francesco Cucca and Daniele Cusi and Deary, {Ian J.} and Dedoussis, {George V.} and {van Duijn}, {Cornelia M.} and Eriksson, {Johan G.} and Barbara Franke and Lude Franke and Paolo Gasparini and Gejman, {Pablo V.} and Christian Gieger and Grabe, {Hans-J. rgen} and Jacob Gratten and Groenen, {Patrick J. F.} and Vilmundur Gudnason and {van der Harst}, Pim and Wolfgang Hoffmann and Elina Hypp{\"o}nen and Iacono, {William G.} and Bo Jacobsson and Marjo-Riitta J{\"a}rvelin and Karl-Heinz J{\"o}ckel and Jaakko Kaprio and Kardia, {Sharon L. R.} and Terho Lehtim{\"a}ki and Lehrer, {Steven F.} and Martin, {Nicholas G.} and Matt McGue and Andres Metspalu and Neil Pendleton and Penninx, {Brenda W. J. H.} and Markus Perola and Nicola Pirastu and Mario Pirastu and Ozren Polasek and Danielle Posthuma and Christine Power and Province, {Michael A.} and Samani, {Nilesh J.} and David Schlessinger and Reinhold Schmidt and S{\o}rensen, {Thorkild I. A.} and Spector, {Tim D.} and Kari Stefansson and Unnur Thorsteinsdottir and Thurik, {A. Roy} and Timpson, {Nicholas J.} and {23andMe Research team} and {Social Science Genetic Association Consortium} and Henning Tiemeier and {Lifelines Cohort Study} and Uitterlinden, {Andr{\'e} G.} and Veronique Vitart and Peter Vollenweider and Weir, {David R.} and Wilson, {James F.} and Wright, {Alan F.} and Conley, {Dalton C.} and Krueger, {Robert F.} and Smith, {George Davey} and Albert Hofman and Laibson, {David I.} and Medland, {Sarah E.} and Jian Yang and Esko, {T. nu} and Chelsea Watson and Jonathan Jala and Dalton Conley and Koellinger, {Philipp D.} and Magnus Johannesson and David Laibson and Meyer, {Michelle N.} and Lee, {James J.} and Augustine Kong and Loic Yengo and David Cesarini and Patrick Turley and Visscher, {Peter M.} and Beauchamp, {Jonathan P.} and Benjamin, {Daniel J.} and Young, {Alexander I.}",

note = "Funding Information: We thank E.M. Tucker-Drob for helpful comments and J. Zeng for help with the SBayesR software. This research was carried out under the auspices of the Social Science Genetic Association Consortium. The analyses reported in the paper fall under National Bureau of Economic Research institutional review board protocols 19_434, 19_465 and 20_041. This paper uses cohort-level data from Okbay et al.62, and information about studies participating in that study can be found in the Additional Acknowledgements Supplementary section of that paper. Per Social Science Genetic Association Consortium policy, we acknowledge the authors of that paper, listed below, as collaborators. 23andMe research participants provided informed consent and participated in the research online, under a protocol approved by the external Association for the Accreditation of Human Research Protection Programs-accredited institutional review board, Ethical & Independent Review Services. Participants were included in the analysis on the basis of consent status as checked at the time data analyses were initiated. We would like to thank the research participants and employees of 23andMe for making this work possible. We gratefully acknowledge the contributions of members of 23andMe{\textquoteright}s Research Team, whose names are listed below. The research has also been conducted using the UKB Resource under application numbers 11425 and 12505. Informed consent was obtained from UKB subjects. Ethical approval for the GS: Scottish Family Health Study was obtained from the Tayside Committee on Medical Research Ethics (on behalf of the National Health Service). H.J, M.B., D. Cesarini and P.T. were supported by the Ragnar S{\"o}derberg Foundation (E42/15 to D. Cesarini); A.O. and P.K. by the European Research Council (consolidator grant 647648 EdGe to P.K.); H.J., M.B., S.M.N., T.G., C.W., J.J., M.N.M., D. Cesarini, P.T., J.P.B., D.J.B. and A.I.Y. by Open Philanthropy (grant 010623-00001 to D.J.B.); R.A. and S.O. by Riksbankens Jubileumsfond (grant P18-0782:1 to S.O.); N.W., G.G., C.W., L.Y. and D.J.B. by the National Institute on Aging (NIA)/National Institutes of Health (NIH) (grants R24-AG065184 and R01-AG042568 to D.J.B.); D.J.B. by the NIA/NIH (grant R56-AG058726 to T. Galama); P.T. by the NIA/National Institute on Mental Health (grants R01-MH101244-02 and U01-MH109539-02 to B. Neale); J.S. and P.M.V. by the Australian Research Council (grant FL180100072 to P.M.V.); and Y.W., L.Y. and P.M.V. by the National Health and Medical Research Council (grant GNT113400 to P.M.V.). The study was also supported by Netherlands Organisation for Scientific Research VENI (grant 016.Veni.198.058 to A.O.); the F.G. Meade Scholarship and UQ Research Training Scholarship from the University of Queensland Senate (Y.W.); the Swedish Research Council (grant 2019-00244 to S.O.); an MRC University Unit Programme Grant (MC_UU_00007/10, QTL in Health and Disease, to C.H.); the Swedish Research Council (grant 421-2013-1061 to M.J.); Pershing Square Fund of the Foundations of Human Behavior (D.L.); the Li Ka Shing Foundation (A.K.); the Australian Research Council (grant DE200100425 to L.Y.); the NIA/NIH (grant K99-AG062787-01 to P.T.); the Government of Canada through Genome Canada and the Ontario Genomics Institute (grant OGI-152 to J.P.B.); the Social Sciences and Humanities Research Council of Canada (J.P.B.); and the Australian Research Council (P.M.V.). Funding Information: We thank E.M. Tucker-Drob for helpful comments and J. Zeng for help with the SBayesR software. This research was carried out under the auspices of the Social Science Genetic Association Consortium. The analyses reported in the paper fall under National Bureau of Economic Research institutional review board protocols 19_434, 19_465 and 20_041. This paper uses cohort-level data from Okbay et al., and information about studies participating in that study can be found in the Additional Acknowledgements Supplementary section of that paper. Per Social Science Genetic Association Consortium policy, we acknowledge the authors of that paper, listed below, as collaborators. 23andMe research participants provided informed consent and participated in the research online, under a protocol approved by the external Association for the Accreditation of Human Research Protection Programs-accredited institutional review board, Ethical & Independent Review Services. Participants were included in the analysis on the basis of consent status as checked at the time data analyses were initiated. We would like to thank the research participants and employees of 23andMe for making this work possible. We gratefully acknowledge the contributions of members of 23andMe{\textquoteright}s Research Team, whose names are listed below. The research has also been conducted using the UKB Resource under application numbers 11425 and 12505. Informed consent was obtained from UKB subjects. Ethical approval for the GS: Scottish Family Health Study was obtained from the Tayside Committee on Medical Research Ethics (on behalf of the National Health Service). H.J, M.B., D. Cesarini and P.T. were supported by the Ragnar S{\"o}derberg Foundation (E42/15 to D. Cesarini); A.O. and P.K. by the European Research Council (consolidator grant 647648 EdGe to P.K.); H.J., M.B., S.M.N., T.G., C.W., J.J., M.N.M., D. Cesarini, P.T., J.P.B., D.J.B. and A.I.Y. by Open Philanthropy (grant 010623-00001 to D.J.B.); R.A. and S.O. by Riksbankens Jubileumsfond (grant P18-0782:1 to S.O.); N.W., G.G., C.W., L.Y. and D.J.B. by the National Institute on Aging (NIA)/National Institutes of Health (NIH) (grants R24-AG065184 and R01-AG042568 to D.J.B.); D.J.B. by the NIA/NIH (grant R56-AG058726 to T. Galama); P.T. by the NIA/National Institute on Mental Health (grants R01-MH101244-02 and U01-MH109539-02 to B. Neale); J.S. and P.M.V. by the Australian Research Council (grant FL180100072 to P.M.V.); and Y.W., L.Y. and P.M.V. by the National Health and Medical Research Council (grant GNT113400 to P.M.V.). The study was also supported by Netherlands Organisation for Scientific Research VENI (grant 016.Veni.198.058 to A.O.); the F.G. Meade Scholarship and UQ Research Training Scholarship from the University of Queensland Senate (Y.W.); the Swedish Research Council (grant 2019-00244 to S.O.); an MRC University Unit Programme Grant (MC_UU_00007/10, QTL in Health and Disease, to C.H.); the Swedish Research Council (grant 421-2013-1061 to M.J.); Pershing Square Fund of the Foundations of Human Behavior (D.L.); the Li Ka Shing Foundation (A.K.); the Australian Research Council (grant DE200100425 to L.Y.); the NIA/NIH (grant K99-AG062787-01 to P.T.); the Government of Canada through Genome Canada and the Ontario Genomics Institute (grant OGI-152 to J.P.B.); the Social Sciences and Humanities Research Council of Canada (J.P.B.); and the Australian Research Council (P.M.V.). Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = apr,

day = "1",

doi = "10.1038/s41588-022-01016-z",

language = "English",

volume = "54",

pages = "437--449",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "4",

}

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals. / 23andMe Research team; Social Science Genetic Association Consortium; Lifelines Cohort Study.

In: Nature Genetics, Vol. 54, No. 4, 01.04.2022, p. 437-449.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

AU - Okbay, Aysu

AU - Wu, Yeda

AU - Wang, Nancy

AU - Jayashankar, Hariharan

AU - Bennett, Michael

AU - Nehzati, Seyed Moeen

AU - Sidorenko, Julia

AU - Kweon, Hyeokmoon

AU - Goldman, Grant

AU - Gjorgjieva, Tamara

AU - Jiang, Yunxuan

AU - Hicks, Barry

AU - Tian, Chao

AU - Hinds, David A.

AU - Ahlskog, Rafael

AU - Magnusson, Patrik K. E.

AU - Oskarsson, Sven

AU - Hayward, Caroline

AU - Campbell, Archie

AU - Porteous, David J.

AU - Freese, Jeremy

AU - Herd, Pamela

AU - Agee, Michelle

AU - Alipanahi, Babak

AU - Auton, Adam

AU - Bell, Robert K.

AU - Bryc, Katarzyna

AU - Elson, Sarah L.

AU - Fontanillas, Pierre

AU - Furlotte, Nicholas A.

AU - Hinds, David A.

AU - Huber, Karen E.

AU - Kleinman, Aaron

AU - Litterman, Nadia K.

AU - McCreight, Jennifer C.

AU - McIntyre, Matthew H.

AU - Mountain, Joanna L.

AU - Northover, Carrie A. M.

AU - Pitts, Steven J.

AU - Sathirapongsasuti, J. Fah

AU - Sazonova, Olga V.

AU - Shelton, Janie F.

AU - Shringarpure, Suyash

AU - Tung, Joyce Y.

AU - Vacic, Vladimir

AU - Wilson, Catherine H.

AU - Fontana, Mark Alan

AU - Pers, Tune H.

AU - Rietveld, Cornelius A.

AU - Chen, Guo-Bo

AU - Emilsson, Valur

AU - Meddens, S. Fleur W.

AU - Pickrell, Joseph K.

AU - Thom, Kevin

AU - Timshel, Pascal

AU - de Vlaming, Ronald

AU - Abdellaoui, Abdel

AU - Ahluwalia, Tarunveer S.

AU - Bacelis, Jonas

AU - Baumbach, Clemens

AU - Bjornsdottir, Gyda

AU - Brandsma, Johannes H.

AU - Concas, Maria Pina

AU - Derringer, Jaime

AU - Galesloot, Tessel E.

AU - Girotto, Giorgia

AU - Gupta, Richa

AU - Hall, Leanne M.

AU - Harris, Sarah E.

AU - Hofer, Edith

AU - Horikoshi, Momoko

AU - Huffman, Jennifer E.

AU - Kaasik, Kadri

AU - Kalafati, Ioanna P.

AU - Karlsson, Robert

AU - Lahti, Jari

AU - van der Lee, Sven J.

AU - de Leeuw, Christiaan

AU - Lind, Penelope A.

AU - Lindgren, Karl-Oskar

AU - Liu, Tian

AU - Mangino, Massimo

AU - Marten, Jonathan

AU - Mihailov, Evelin

AU - Miller, Michael B.

AU - van der Most, Peter J.

AU - Oldmeadow, Christopher

AU - Payton, Antony

AU - Pervjakova, Natalia

AU - Peyrot, Wouter J.

AU - Qian, Yong

AU - Raitakari, Olli

AU - Rueedi, Rico

AU - Salvi, Erika

AU - Schmidt, B. rge

AU - Schraut, Katharina E.

AU - Shi, Jianxin

AU - Smith, Albert V.

AU - Poot, Raymond A.

AU - Pourcain, Beate St

AU - Teumer, Alexander

AU - Thorleifsson, Gudmar

AU - Verweij, Niek

AU - Vuckovic, Dragana

AU - Wellmann, Juergen

AU - Westra, Harm-Jan

AU - Yang, Jingyun

AU - Zhao, Wei

AU - Zhu, Zhihong

AU - Alizadeh, Behrooz Z.

AU - Amin, Najaf

AU - Bakshi, Andrew

AU - Baumeister, Sebastian E.

AU - Biino, Ginevra

AU - Bønnelykke, Klaus

AU - Boyle, Patricia A.

AU - Campbell, Harry

AU - Cappuccio, Francesco P.

AU - Davies, Gail

AU - de Neve, Jan-Emmanuel

AU - Deloukas, Panos

AU - Demuth, Ilja

AU - Ding, Jun

AU - Eibich, Peter

AU - Eisele, Lewin

AU - Eklund, Niina

AU - Evans, David M.

AU - Faul, Jessica D.

AU - Feitosa, Mary F.

AU - Forstner, Andreas J.

AU - Gandin, Ilaria

AU - Gunnarsson, Bjarni

AU - Halldórsson, Bjarni V.

AU - Harris, Tamara B.

AU - Heath, Andrew C.

AU - Hocking, Lynne J.

AU - Holliday, Elizabeth G.

AU - Homuth, Georg

AU - Horan, Michael A.

AU - Hottenga, Jouke-Jan

AU - de Jager, Philip L.

AU - Joshi, Peter K.

AU - Jugessur, Astanand

AU - Kaakinen, Marika A.

AU - Kähönen, Mika

AU - Kanoni, Stavroula

AU - Keltigangas-Järvinen, Liisa

AU - Kiemeney, Lambertus A. L. M.

AU - Kolcic, Ivana

AU - Koskinen, Seppo

AU - Kraja, Aldi T.

AU - Kroh, Martin

AU - Kutalik, Zoltan

AU - Latvala, Antti

AU - Launer, Lenore J.

AU - Lebreton, Maël P.

AU - Levinson, Douglas F.

AU - Lichtenstein, Paul

AU - Lichtner, Peter

AU - Liewald, David C. M.

AU - Loukola, Anu

AU - Madden, Pamela A.

AU - Mägi, Reedik

AU - Mäki-Opas, Tomi

AU - Marioni, Riccardo E.

AU - Marques-Vidal, Pedro

AU - Meddens, Gerardus A.

AU - McMahon, George

AU - Meisinger, Christa

AU - Meitinger, Thomas

AU - Milaneschi, Yusplitri

AU - Milani, Lili

AU - Montgomery, Grant W.

AU - Myhre, Ronny

AU - Nelson, Christopher P.

AU - Nyholt, Dale R.

AU - Ollier, William E. R.

AU - Palotie, Aarno

AU - Paternoster, Lavinia

AU - Pedersen, Nancy L.

AU - Petrovic, Katja E.

AU - Räikkönen, Katri

AU - Ring, Susan M.

AU - Robino, Antonietta

AU - Rostapshova, Olga

AU - Rudan, Igor

AU - Rustichini, Aldo

AU - Salomaa, Veikko

AU - Sanders, Alan R.

AU - Sarin, Antti-Pekka

AU - Schmidt, Helena

AU - Scott, Rodney J.

AU - Smith, Blair H.

AU - Smith, Jennifer A.

AU - Staessen, Jan A.

AU - Steinhagen-Thiessen, Elisabeth

AU - Strauch, Konstantin

AU - Terracciano, Antonio

AU - Tobin, Martin D.

AU - Ulivi, Sheila

AU - Vaccargiu, Simona

AU - Quaye, Lydia

AU - van Rooij, Frank J. A.

AU - Venturini, Cristina

AU - Vinkhuyzen, Anna A. E.

AU - Völker, Uwe

AU - Völzke, Henry

AU - Vonk, Judith M.

AU - Vozzi, Diego

AU - Waage, Johannes

AU - Ware, Erin B.

AU - Willemsen, Gonneke

AU - Attia, John R.

AU - Bennett, David A.

AU - Berger, Klaus

AU - Bertram, Lars

AU - Bisgaard, Hans

AU - Boomsma, Dorret I.

AU - Borecki, Ingrid B.

AU - Bültmann, Ute

AU - Chabris, Christopher F.

AU - Cucca, Francesco

AU - Cusi, Daniele

AU - Deary, Ian J.

AU - Dedoussis, George V.

AU - van Duijn, Cornelia M.

AU - Eriksson, Johan G.

AU - Franke, Barbara

AU - Franke, Lude

AU - Gasparini, Paolo

AU - Gejman, Pablo V.

AU - Gieger, Christian

AU - Grabe, Hans-J. rgen

AU - Gratten, Jacob

AU - Groenen, Patrick J. F.

AU - Gudnason, Vilmundur

AU - van der Harst, Pim

AU - Hoffmann, Wolfgang

AU - Hyppönen, Elina

AU - Iacono, William G.

AU - Jacobsson, Bo

AU - Järvelin, Marjo-Riitta

AU - Jöckel, Karl-Heinz

AU - Kaprio, Jaakko

AU - Kardia, Sharon L. R.

AU - Lehtimäki, Terho

AU - Lehrer, Steven F.

AU - Martin, Nicholas G.

AU - McGue, Matt

AU - Metspalu, Andres

AU - Pendleton, Neil

AU - Penninx, Brenda W. J. H.

AU - Perola, Markus

AU - Pirastu, Nicola

AU - Pirastu, Mario

AU - Polasek, Ozren

AU - Posthuma, Danielle

AU - Power, Christine

AU - Province, Michael A.

AU - Samani, Nilesh J.

AU - Schlessinger, David

AU - Schmidt, Reinhold

AU - Sørensen, Thorkild I. A.

AU - Spector, Tim D.

AU - Stefansson, Kari

AU - Thorsteinsdottir, Unnur

AU - Thurik, A. Roy

AU - Timpson, Nicholas J.

AU - 23andMe Research team

AU - Social Science Genetic Association Consortium

AU - Tiemeier, Henning

AU - Lifelines Cohort Study

AU - Uitterlinden, André G.

AU - Vitart, Veronique

AU - Vollenweider, Peter

AU - Weir, David R.

AU - Wilson, James F.

AU - Wright, Alan F.

AU - Conley, Dalton C.

AU - Krueger, Robert F.

AU - Smith, George Davey

AU - Hofman, Albert

AU - Laibson, David I.

AU - Medland, Sarah E.

AU - Yang, Jian

AU - Esko, T. nu

AU - Watson, Chelsea

AU - Jala, Jonathan

AU - Conley, Dalton

AU - Koellinger, Philipp D.

AU - Johannesson, Magnus

AU - Laibson, David

AU - Meyer, Michelle N.

AU - Lee, James J.

AU - Kong, Augustine

AU - Yengo, Loic

AU - Cesarini, David

AU - Turley, Patrick

AU - Visscher, Peter M.

AU - Beauchamp, Jonathan P.

AU - Benjamin, Daniel J.

AU - Young, Alexander I.

N1 - Funding Information: We thank E.M. Tucker-Drob for helpful comments and J. Zeng for help with the SBayesR software. This research was carried out under the auspices of the Social Science Genetic Association Consortium. The analyses reported in the paper fall under National Bureau of Economic Research institutional review board protocols 19_434, 19_465 and 20_041. This paper uses cohort-level data from Okbay et al.62, and information about studies participating in that study can be found in the Additional Acknowledgements Supplementary section of that paper. Per Social Science Genetic Association Consortium policy, we acknowledge the authors of that paper, listed below, as collaborators. 23andMe research participants provided informed consent and participated in the research online, under a protocol approved by the external Association for the Accreditation of Human Research Protection Programs-accredited institutional review board, Ethical & Independent Review Services. Participants were included in the analysis on the basis of consent status as checked at the time data analyses were initiated. We would like to thank the research participants and employees of 23andMe for making this work possible. We gratefully acknowledge the contributions of members of 23andMe’s Research Team, whose names are listed below. The research has also been conducted using the UKB Resource under application numbers 11425 and 12505. Informed consent was obtained from UKB subjects. Ethical approval for the GS: Scottish Family Health Study was obtained from the Tayside Committee on Medical Research Ethics (on behalf of the National Health Service). H.J, M.B., D. Cesarini and P.T. were supported by the Ragnar Söderberg Foundation (E42/15 to D. Cesarini); A.O. and P.K. by the European Research Council (consolidator grant 647648 EdGe to P.K.); H.J., M.B., S.M.N., T.G., C.W., J.J., M.N.M., D. Cesarini, P.T., J.P.B., D.J.B. and A.I.Y. by Open Philanthropy (grant 010623-00001 to D.J.B.); R.A. and S.O. by Riksbankens Jubileumsfond (grant P18-0782:1 to S.O.); N.W., G.G., C.W., L.Y. and D.J.B. by the National Institute on Aging (NIA)/National Institutes of Health (NIH) (grants R24-AG065184 and R01-AG042568 to D.J.B.); D.J.B. by the NIA/NIH (grant R56-AG058726 to T. Galama); P.T. by the NIA/National Institute on Mental Health (grants R01-MH101244-02 and U01-MH109539-02 to B. Neale); J.S. and P.M.V. by the Australian Research Council (grant FL180100072 to P.M.V.); and Y.W., L.Y. and P.M.V. by the National Health and Medical Research Council (grant GNT113400 to P.M.V.). The study was also supported by Netherlands Organisation for Scientific Research VENI (grant 016.Veni.198.058 to A.O.); the F.G. Meade Scholarship and UQ Research Training Scholarship from the University of Queensland Senate (Y.W.); the Swedish Research Council (grant 2019-00244 to S.O.); an MRC University Unit Programme Grant (MC_UU_00007/10, QTL in Health and Disease, to C.H.); the Swedish Research Council (grant 421-2013-1061 to M.J.); Pershing Square Fund of the Foundations of Human Behavior (D.L.); the Li Ka Shing Foundation (A.K.); the Australian Research Council (grant DE200100425 to L.Y.); the NIA/NIH (grant K99-AG062787-01 to P.T.); the Government of Canada through Genome Canada and the Ontario Genomics Institute (grant OGI-152 to J.P.B.); the Social Sciences and Humanities Research Council of Canada (J.P.B.); and the Australian Research Council (P.M.V.). Funding Information: We thank E.M. Tucker-Drob for helpful comments and J. Zeng for help with the SBayesR software. This research was carried out under the auspices of the Social Science Genetic Association Consortium. The analyses reported in the paper fall under National Bureau of Economic Research institutional review board protocols 19_434, 19_465 and 20_041. This paper uses cohort-level data from Okbay et al., and information about studies participating in that study can be found in the Additional Acknowledgements Supplementary section of that paper. Per Social Science Genetic Association Consortium policy, we acknowledge the authors of that paper, listed below, as collaborators. 23andMe research participants provided informed consent and participated in the research online, under a protocol approved by the external Association for the Accreditation of Human Research Protection Programs-accredited institutional review board, Ethical & Independent Review Services. Participants were included in the analysis on the basis of consent status as checked at the time data analyses were initiated. We would like to thank the research participants and employees of 23andMe for making this work possible. We gratefully acknowledge the contributions of members of 23andMe’s Research Team, whose names are listed below. The research has also been conducted using the UKB Resource under application numbers 11425 and 12505. Informed consent was obtained from UKB subjects. Ethical approval for the GS: Scottish Family Health Study was obtained from the Tayside Committee on Medical Research Ethics (on behalf of the National Health Service). H.J, M.B., D. Cesarini and P.T. were supported by the Ragnar Söderberg Foundation (E42/15 to D. Cesarini); A.O. and P.K. by the European Research Council (consolidator grant 647648 EdGe to P.K.); H.J., M.B., S.M.N., T.G., C.W., J.J., M.N.M., D. Cesarini, P.T., J.P.B., D.J.B. and A.I.Y. by Open Philanthropy (grant 010623-00001 to D.J.B.); R.A. and S.O. by Riksbankens Jubileumsfond (grant P18-0782:1 to S.O.); N.W., G.G., C.W., L.Y. and D.J.B. by the National Institute on Aging (NIA)/National Institutes of Health (NIH) (grants R24-AG065184 and R01-AG042568 to D.J.B.); D.J.B. by the NIA/NIH (grant R56-AG058726 to T. Galama); P.T. by the NIA/National Institute on Mental Health (grants R01-MH101244-02 and U01-MH109539-02 to B. Neale); J.S. and P.M.V. by the Australian Research Council (grant FL180100072 to P.M.V.); and Y.W., L.Y. and P.M.V. by the National Health and Medical Research Council (grant GNT113400 to P.M.V.). The study was also supported by Netherlands Organisation for Scientific Research VENI (grant 016.Veni.198.058 to A.O.); the F.G. Meade Scholarship and UQ Research Training Scholarship from the University of Queensland Senate (Y.W.); the Swedish Research Council (grant 2019-00244 to S.O.); an MRC University Unit Programme Grant (MC_UU_00007/10, QTL in Health and Disease, to C.H.); the Swedish Research Council (grant 421-2013-1061 to M.J.); Pershing Square Fund of the Foundations of Human Behavior (D.L.); the Li Ka Shing Foundation (A.K.); the Australian Research Council (grant DE200100425 to L.Y.); the NIA/NIH (grant K99-AG062787-01 to P.T.); the Government of Canada through Genome Canada and the Ontario Genomics Institute (grant OGI-152 to J.P.B.); the Social Sciences and Humanities Research Council of Canada (J.P.B.); and the Australian Research Council (P.M.V.). Publisher Copyright: © 2022, The Author(s).

PY - 2022/4/1

Y1 - 2022/4/1

N2 - We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12–16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI’s magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.

AB - We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12–16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI’s magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85127422477&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/35361970

U2 - 10.1038/s41588-022-01016-z

DO - 10.1038/s41588-022-01016-z

M3 - Article

C2 - 35361970

SN - 1061-4036

VL - 54

SP - 437

EP - 449

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

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