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 › peer-review

220 Scopus citations

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
State	Published - Apr 2022

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10.1038/s41588-022-01016-z

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@article{585f3ec52b4044e28ab53bcd9e89e4cd,

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 = "{23andMe Research Team} and {Social Science Genetic Association Consortium} and {Lifelines Cohort Study} and 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 Chen, {Guo Bo} 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 Lindgren, {Karl Oskar} 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 B{\"o}rge Schmidt 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 Westra, {Harm Jan} 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 Hottenga, {Jouke Jan} 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 Sarin, {Antti Pekka} 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 Province, {Michael A.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = apr,

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

language = "English",

volume = "54",

pages = "437--449",

journal = "Nature Genetics",

issn = "1061-4036",

number = "4",

}

TY - JOUR

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

AU - 23andMe Research Team

AU - Social Science Genetic Association Consortium

AU - Lifelines Cohort Study

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, Börge

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 - Province, Michael A.

PY - 2022/4

Y1 - 2022/4

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 - http://www.scopus.com/inward/record.url?scp=85127422477&partnerID=8YFLogxK

U2 - 10.1038/s41588-022-01016-z

DO - 10.1038/s41588-022-01016-z

M3 - Article

C2 - 35361970

AN - SCOPUS:85127422477

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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