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

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 1...

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Published in:Nature genetics Vol. 54; no. 4; pp. 437 - 449
Main Authors: Okbay, Aysu, Wu, Yeda, Wang, Nancy, Jayashankar, Hariharan, Bennett, Michael, Nehzati, Seyed Moeen, Sidorenko, Julia, Kweon, Hyeokmoon, Goldman, Grant, Gjorgjieva, Tamara, Jiang, Yunxuan, Hicks, Barry, Tian, Chao, Hinds, David A., Ahlskog, Rafael, Magnusson, Patrik K. E., Oskarsson, Sven, Hayward, Caroline, Campbell, Archie, Porteous, David J., Freese, Jeremy, Herd, Pamela, Watson, Chelsea, Jala, Jonathan, Conley, Dalton, Koellinger, Philipp D., Johannesson, Magnus, Laibson, David, Meyer, Michelle N., Lee, James J., Kong, Augustine, Yengo, Loic, Cesarini, David, Turley, Patrick, Visscher, Peter M., Beauchamp, Jonathan P., Benjamin, Daniel J., Young, Alexander I.
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01.04.2022
Nature Publishing Group
Subjects:
631/208/1515
631/208/205/2138
Agriculture
Animal Genetics and Genomics
Biomedical and Life Sciences
Biomedicine
Cancer Research
Education
Educational attainment
Gene Function
genetics
Genome-wide association studies
Genome-Wide Association Study
Genomes
Genotype & phenotype
Gynaecology, Obstetrics and Reproductive Medicine
Gynekologi, obstetrik och reproduktionsmedicin
Human Genetics
Humans
Meta-analysis
Multifactorial Inheritance
Multifactorial Inheritance - genetics
Nucleotides
Phenotypes
Polymorphism
Polymorphism, Single Nucleotide - genetics
Quantitative genetics
Single Nucleotide
Single-nucleotide polymorphism
X chromosomes
ISSN:1061-4036, 1546-1718, 1546-1718
Online Access:Get full text
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Summary: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. A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.
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ISSN:1061-4036
1546-1718
1546-1718
DOI:10.1038/s41588-022-01016-z