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

• 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
• DOI: 10.1038/s41588-022-01016-z

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.