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Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals
Aysu Okbay, Yeda Wu, Nancy Wang, Hariharan Jayashankar, Michael Bennett, Seyed Moeen Nehzati, Julia Sidorenko, Hyeokmoon Kweon, Grant Goldman, Tamara Gjorgjieva, Yunxuan Jiang, Barry Hicks, Chao Tian, David A. Hinds, Rafael Ahlskog, Patrik K. E. Magnusson, Sven Oskarsson, Caroline Hayward, Archie Campbell, David J. Porteous, Jeremy Freese, Pamela Herd, Michelle Agee, Babak Alipanahi, Adam Auton, Robert K. Bell, Katarzyna Bryc, Sarah L. Elson, Pierre Fontanillas, Nicholas A. Furlotte, Karen E. Huber, Aaron Kleinman, Nadia K. Litterman, Jennifer C. McCreight, Matthew H. McIntyre, Joanna L. Mountain, Carrie A. M. Northover, Steven J. Pitts, J. Fah Sathirapongsasuti, Olga V. Sazonova, Janie F. Shelton, Suyash Shringarpure, Joyce Y. Tung, Vladimir Vacic, Catherine H. Wilson, Mark Alan Fontana, Tune H. Pers, Cornelius A. Rietveld, Guo‐Bo Chen, Valur Emilsson, S. Fleur W. Meddens, Joseph K. Pickrell, Kevin Thom, Pascal Timshel, Ronald de Vlaming, Abdel Abdellaoui, Tarunveer S. Ahluwalia, Jonas Bačelis, Clemens Baumbach, Gyða Björnsdóttir, J Brandsma, Maria Pina Concas, Jaime Derringer, Tessel E. Galesloot, Giorgia Girotto, Richa Gupta, Leanne M. Hall, Sarah E. Harris, Edith Hofer, Momoko Horikoshi, Jennifer E. Huffman, Kadri Kaasik, Ioanna Panagiota Kalafati, Robert Karlsson, Jari Lahti, Sven J. van der Lee, Christiaan de Leeuw, Penelope A. Lind, Karl‐Oskar Lindgren, Tian Liu, Massimo Mangino, Jonathan Marten, Evelin Mihailov, Michael Miller, Peter J. van der Most, Christopher Oldmeadow, Antony Payton, Natalia Pervjakova, Wouter J. Peyrot, Yong Qian, Olli T. Raitakari, Rico Rueedi, Erika Salvi, Börge Schmidt, Katharina E. Schraut, Jianxin Shi, Albert V. Smith, Raymond A. Poot, Beaté St Pourcain, Alexander Teumer, Guðmar Þorleifsson, Niek Verweij, Dragana Vuckovic, Juergen Wellmann, Harm-Jan Westra, Jingyun Yang, Wei Zhao, Zhihong Zhu, Behrooz Z. Alizadeh, Najaf Amin, Andrew Bakshi, Sebastian E. Baumeister, Ginevra Biino, Klaus Bønnelykke, Patricia A. Boyle, Harry Campbell, Francesco P. Cappuccio, Gail Davies, Jan-Emmanuel De Neve, Panos Deloukas, Ilja Demuth, Jun Ding, Peter Eibich, Lewin Eisele, Niina Eklund, David M. Evans, Jessica D. Faul, Mary F. Feitosa, Andreas J. Forstner, Ilaria Gandin, Bjarni Gunnarsson, Bjarni V. Halldórsson, Tamara B. Harris, Andrew C. Heath, Lynne J. Hocking, Georg Homuth, Michael A. Horan, Jouke‐Jan Hottenga, Philip L. De Jager, Peter K. Joshi, Astanand Jugessur, Marika Kaakinen, Mika Kähönen, Stavroula Kanoni, Liisa Keltigangas-Järvinen, Lambertus A. Kiemeney, Ivana Kolčić, Seppo Koskinen, Aldi T. Kraja, Martin Kroh, Zoltán Kutalik, Antti Latvala, Lenore J. Launer, Maël P. Lebreton, Douglas F. Levinson, Paul Lichtenstein, Peter Lichtner, David C. Liewald, Anu Loukola, Pamela A. F. Madden, Reedik Mägi, Tomi Mäki‐Opas, Riccardo E. Marioni, Pedro Marques‐Vidal, Gerardus A. Meddens, George McMahon, Christa Meisinger, Thomas Meitinger, Yusplitri Milaneschi, Lili Milani, Grant W. Montgomery, Ronny Myhre, Christopher P. Nelson, Dale R. Nyholt, William Ollier, Aarno Palotie, Lavinia Paternoster, Nancy L. Pedersen, Katja Petrovic, Katri Räikkönen, Susan M. Ring, Antonietta Robino, Olga Rostapshova, Igor Rudan, Aldo Rustichini, Veikko Salomaa, Alan R. Sanders, Antti‐Pekka Sarin, Helena Schmidt, Rodney J. Scott, Blair H. Smith, Jennifer A. Smith, Jan A. Staessen, Elisabeth Steinhagen–Thiessen, Konstantin Strauch, Antonio Terracciano, Martin D. Tobin, Sheila Ulivi, Simona Vaccargiu, Lydia Quaye, Frank J.A. van Rooij, Cristina Venturini, Anna A. E. Vinkhuyzen, Uwe Völker, Henry Völzke, Judith M. Vonk, Diego Vozzi, Johannes Waage, Erin B. Ware, Gonneke Willemsen, John Attia, David A. Bennett, Lars Bertram, Hans Bisgaard, Dorret I. Boomsma, Ingrid B. Borecki, Ute Bültmann, Christopher F. Chabris, Francesco Cucca, Daniele Cusi, Ian J. Deary, George Dedoussis, Cornelia M. van Duijn, Johan G. Eriksson, Barbara Franke, Lude Franke, Paolo Gasparini, Pablo V. Gejman, Christian Gieger, Hans J. Grabe, Jacob Gratten, Patrick J. F. Groenen, Vilmundur Guðnason, Pim van der Harst, Wolfgang Hoffmann, Elina Hyppönen, William G. Iacono, Bo Jacobsson, Marjo‐Riitta Järvelin, Karl‐Heinz Jöckel, Jaakko Kaprio, Sharon L. R. Kardia, Terho Lehtimäki, Steven F. Lehrer, Nicholas G. Martin, Matt McGue, Andres Metspalu, Neil Pendleton, Brenda W.J.H. Penninx, Markus Perola, Nicola Pirastu, Mario Pirastu, Ozren Polašek, Daniëlle Posthuma, Christopher Power, Michael A. Province, Nilesh J. Samani, David Schlessinger, Reinhold Schmidt, Thorkild I. A. Sørensen, Tim D. Spector, Kāri Stefánsson, Unnur Þorsteinsdóttir, Roy Thurik, Nicholas J. Timpson, Henning Tiemeier, André G. Uitterlinden, Véronique Vitart, Péter Vollenweider, David R. Weir, James F. Wilson, Alan F. Wright, Dalton Conley, Robert F. Krueger, George Davey Smith, Albert Hofman, David Laibson, Sarah E. Medland, Jian Yang, Tõnu Esko, Chelsea Watson, Jonathan Jala, Philipp Koellinger, Magnus Johannesson, Michelle N. Meyer, James J. Lee, Augustine Kong, Loïc Yengo, David Cesarini, Patrick Turley, Peter M. Visscher, Jonathan Beauchamp, Daniel J. Benjamin, Alexander I. Young
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.
Bibliographic record
VenueNature Genetics · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsQueen's UniversityUniversity of Toronto
FundersNational Health and Medical Research CouncilAustralian Research CouncilMedical Research CouncilNational Institute of Mental HealthSocial Sciences and Humanities Research Council of CanadaOulun YliopistoDepartment of Education and TrainingRiksbankens JubileumsfondVetenskapsrådetGenome CanadaLundbeckfondenErasmus Universiteit RotterdamUniversity of South AustraliaUniversity of QueenslandNational Institutes of HealthOpen Philanthropy ProjectNetherlands Heart InstituteImperial College LondonOntario Genomics InstituteNederlandse Organisatie voor Wetenschappelijk OnderzoekLi Ka Shing FoundationSteno Diabetes Center CopenhagenNational Institute on AgingPershing Square FoundationEconomic and Social Research CouncilU.S. Department of Health and Human ServicesSchool of Public Health, Imperial College LondonOntario GenomicsRagnar Söderbergs stiftelseGovernment of Canada
KeywordsGenome-wide association studyBiologySingle-nucleotide polymorphismGeneticsGenetic associationGenomeMultifactorial InheritanceGenotypeGene
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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.011
Threshold uncertainty score0.526
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
Opus teacher head0.014
GPT teacher head0.288
Teacher spread0.274 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itQuick stats
Citations689
Published2022
Admission routes2
Has abstractyes