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

TitleGene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.
Publication TypeJournal Article
Year of Publication2018
AuthorsLee, JJ, Wedow, R, Okbay, A, Kong, E, Maghzian, O, Zacher, M, Nguyen-Viet, TAnh, Bowers, P, Sidorenko, J, Linnér, RKarlsson, Fontana, MAlan, Kundu, T, Lee, C, Li, H, Li, R, Royer, R, Timshel, PN, Walters, RK, Willoughby, EA, Yengo, L, Alver, M, Bao, Y, Clark, DW, Day, FR, Furlotte, NA, Joshi, PK, Kemper, KE, Kleinman, A, Langenberg, C, Mägi, R, Trampush, JW, Verma, SSetia, Wu, Y, Lam, M, Zhao, JHua, Zheng, Z, Boardman, JD, Campbell, H, Freese, J, Harris, KMullan, Hayward, C, Herd, P, Kumari, M, Lencz, T, Luan, J'an, Malhotra, AK, Metspalu, A, Milani, L, Ong, KK, Perry, JRB, Porteous, DJ, Ritchie, MD, Smart, MC, Smith, BH, Tung, JY, Wareham, NJ, Wilson, JF, Beauchamp, JP, Conley, DC, Esko, T, Lehrer, SF, Magnusson, PKE, Oskarsson, S, Pers, TH, Robinson, MR, Thom, K, Watson, C, Chabris, CF, Meyer, MN, Laibson, DI, Yang, J, Johannesson, M, Koellinger, PD, Turley, P, Visscher, PM, Benjamin, DJ, Cesarini, D
Corporate Authors23andMe Research Team, COGENT (Cognitive Genomics Consortium), Social Science Genetic Association Consortium
JournalNature Genetics
Volume50
Issue8
Pagination1112-1121
Date Published2018 07 23
ISSN Number1546-1718
KeywordsAdult, Aged, Aged, 80 and over, Cohort Studies, Educational Status, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Multifactorial Inheritance, Phenotype, Polymorphism, Single Nucleotide
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.

DOI10.1038/s41588-018-0147-3
User Guide Notes

http://www.ncbi.nlm.nih.gov/pubmed/30038396?dopt=Abstract

Alternate JournalNat. Genet.
Citation Key10712
PubMed ID30038396
PubMed Central IDPMC6393768
Grant ListG1001799 / MRC_ / Medical Research Council / United Kingdom
MR/N01104X/2 / MRC_ / Medical Research Council / United Kingdom
R01 HD073342 / HD / NICHD NIH HHS / United States
MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom
MC_UU_12015/1 / MRC_ / Medical Research Council / United Kingdom
P30 AG010161 / AG / NIA NIH HHS / United States
R01 AG055406 / AG / NIA NIH HHS / United States
/ WT_ / Wellcome Trust / United Kingdom
R01 AG015819 / AG / NIA NIH HHS / United States
647648 / ERC_ / European Research Council / International
MC_UU_12015/2 / MRC_ / Medical Research Council / United Kingdom
P2C HD047879 / HD / NICHD NIH HHS / United States
P2C HD066613 / HD / NICHD NIH HHS / United States
BB/F019394/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
P01 AG005842 / AG / NIA NIH HHS / United States
P2C HD050924 / HD / NICHD NIH HHS / United States
G0600237 / MRC_ / Medical Research Council / United Kingdom
G0100594 / MRC_ / Medical Research Council / United Kingdom
P30 AG012810 / AG / NIA NIH HHS / United States
R01 AG042568 / AG / NIA NIH HHS / United States
T32 AG000186 / AG / NIA NIH HHS / United States
BB/F022441/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
G0901461 / MRC_ / Medical Research Council / United Kingdom