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Record W2883573930 · doi:10.1038/s41588-018-0147-3

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

2018· review· en· W2883573930 on OpenAlexaff
James J. Lee, Robbee Wedow, Aysu Okbay, Edward Kong, Omeed Maghzian, Meghan Zacher, Tuan Anh Nguyen-Viet, Peter N. Bowers, Julia Sidorenko, Richard Karlsson Linnér, Mark Alan Fontana, Tushar Kundu, Chan Wook Lee, Hui Li, Ruoxi Li, Rebecca Royer, Pascal Timshel, Raymond K. Walters, Emily A. Willoughby, Loïc Yengo, Maris Alver, Yanchun Bao, David W. Clark, Felix R. Day, Nicholas A. Furlotte, Peter K. Joshi, Kathryn E. Kemper, Aaron Kleinman, Claudia Langenberg, Reedik Mägi, Joey W. Trampush, Shefali S. Verma, Yang Wu, Max Lam, Jing Hua Zhao, Zhili Zheng, Harry Campbell, Jeremy Freese, Kathleen Mullan Harris, Caroline Hayward, Pamela Herd, Meena Kumari, Todd Lencz, Jian’an Luan, Anil K. Malhotra, Andres Metspalu, Lili Milani, Ken K. Ong, John R. B. Perry, David J. Porteous, Marylyn D. Ritchie, Melissa Smart, Blair H. Smith, Joyce Y. Tung, Nicholas J. Wareham, James F. Wilson, Jonathan Beauchamp, Dalton Conley, Tõnu Esko, Steven F. Lehrer, Patrik K. E. Magnusson, Sven Oskarsson, Tune H. Pers, Matthew R. Robinson, Kevin Thom, Chelsea Watson, Christopher F. Chabris, Michelle N. Meyer, David Laibson, Jian Yang, Magnus Johannesson, Philipp Koellinger, Patrick Turley, Peter M. Visscher, Daniel J. Benjamin, David Cesarini

Bibliographic record

VenueNature Genetics · 2018
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsQueen's UniversityUniversity of Toronto
FundersNational Institute on AgingEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentEconomic and Social Research CouncilBiotechnology and Biological Sciences Research CouncilMedical Research CouncilLundbeckfondenKarolinska InstitutetNational Institute for Health and Care ResearchNovo Nordisk FondenOpen Philanthropy ProjectNational Institutes of HealthNational Institute of Mental HealthVetenskapsrådetWellcome Trust
KeywordsGenome-wide association studyBiologySingle-nucleotide polymorphismEducational attainmentMultifactorial InheritanceHeritabilityGenetic associationGeneticsSNPGeneGenotype

Abstract

fetched live from OpenAlex

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.

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.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.004
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.003
Threshold uncertainty score0.011

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.004
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0030.002
Science and technology studies0.0000.001
Scholarly communication0.0010.001
Open science0.0010.001
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0020.001

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 head0.013
GPT teacher head0.303
Teacher spread0.290 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2,846
Published2018
Admission routes1
Has abstractyes

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