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

Lee, J. J., Wedow, R., Okbay, A., Kong, E., Maghzian, O., Zacher, M., Nguyen-Viet, T. A., Bowers, P., Sidorenko, J., Linnér, R. K., Fontana, M. A., Kundu, T., Lee, C., Li, H., Li, R., Royer, R., Timshel, P. N., Walters, R. K., Willoughby, E. A., Yengo, L. and 57 moreLee, J. J., Wedow, R., Okbay, A., Kong, E., Maghzian, O., Zacher, M., Nguyen-Viet, T. A., Bowers, P., Sidorenko, J., Linnér, R. K., Fontana, M. A., Kundu, T., Lee, C., Li, H., Li, R., Royer, R., Timshel, P. N., Walters, R. K., Willoughby, E. A., Yengo, L., 23andMe Research Team, COGENT (Cognitive Genomics Consortium), Social Science Genetic Association Consortium, Alver, M., Bao, Y., Clark, D. W., Day, F. R., Furlotte, N. A., Joshi, P. K., Kemper, K. E., Kleinman, A., Langenberg, C., Mägi, R., Trampush, J. W., Verma, S. S., Wu, Y., Lam, M., Zhao, J. H., Zheng, Z., Boardman, J. D., Campbell, H., Freese, J., Harris, K. M., Hayward, C., Herd, P., Kumari, M., Lencz, T., Luan, J., Malhotra, A. K., Metspalu, A., Milani, L., Ong, K. K., Perry, J. R. B., Porteous, D. J., Ritchie, M. D., Smart, M. C., Smith, B. H., Tung, J. Y., Wareham, N. J., Wilson, J. F., Beauchamp, J. P., Conley, D. C., Esko, T., Lehrer, S. F., Magnusson, P. K. E., Oskarsson, S., Pers, T. H., Robinson, M. R., Thom, K., Watson, C., Chabris, C. F., Meyer, M. N., Laibson, D. I., Yang, J., Johannesson, M., Koellinger, P. D., Turley, P., Visscher, P. M., Benjamin, D. J., & 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. doi:10.1038/s41588-018-0147-3.
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.
Publication type
Journal article
Publication date
2018

Share this page