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

23andMe Research Team, James J. Lee, Robbee Wedow, Aysu Okbay, Edward Kong, Omeed Maghzian, Meghan Zacher, Tuan Anh Nguyen-Viet, Peter Bowers, Julia Sidorenko, Richard Karlsson Linnér, Mark Alan Fontana, Tushar Kundu, Chanwook Lee, Hui Li, Ruoxi Li, Rebecca Royer, Pascal N. Timshel, Raymond K Walters, Emily A. WilloughbyLoïc 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 Setia Verma, Yang Wu, Max Lam, Jing Hua Zhao, Zhili Zheng, Jason D. Boardman, 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, Blair H Smith, John R. B. Perry, David J. Porteous, Marylyn D. Ritchie, Melissa C. Smart, Joyce Y. Tung, Nicholas J. Wareham, James F. Wilson, Jonathan P. 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 D. Koellinger, Patrick Turley, Peter M. Visscher, Daniel J. Benjamin, David Cesarini

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Abstract

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.

Original languageEnglish
Pages (from-to)1112-1121
Number of pages10
JournalNature Genetics
Volume50
Issue number8
DOIs
Publication statusPublished - 23 Jul 2018

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    23andMe Research Team, Lee, J. J., Wedow, R., Okbay, A., Kong, E., Maghzian, O., Zacher, M., Nguyen-Viet, T. A., Bowers, P., Sidorenko, J., Karlsson Linnér, R., Fontana, M. A., Kundu, T., Lee, C., Li, H., Li, R., Royer, R., Timshel, P. N., Walters, R. K., ... Cesarini, D. (2018). Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals. Nature Genetics, 50(8), 1112-1121. https://doi.org/10.1038/s41588-018-0147-3