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

被引：1551

作者：

Lee, James J. ^{[1
]}

Wedow, Robbee ^{[2
,3
,4
]}

Okbay, Aysu ^{[5
,6
]}

Kong, Edward ^{[7
]}

Maghzian, Omeed ^{[7
]}

Zacher, Meghan ^{[8
]}

Tuan Anh Nguyen-Viet ^{[9
]}

Bowers, Peter ^{[7
]}

Sidorenko, Julia ^{[10
,11
]}

Linner, Richard Karlsson ^{[5
,6
]}

Fontana, Mark Alan ^{[13
]}

Kundu, Tushar ^{[9
]}

Lee, Chanwook ^{[7
]}

Li, Hui ^{[7
]}

Li, Ruoxi ^{[9
]}

Royer, Rebecca ^{[9
]}

Timshel, Pascal N. ^{[14
,15
]}

Walters, Raymond K. ^{[16
,17
]}

Willoughby, Emily A. ^{[1
]}

Yengo, Loic ^{[10
]}

Alver, Maris ^{[11
]}

Bao, Yanchun ^{[18
]}

Clark, David W. ^{[19
]}

Day, Felix R. ^{[20
]}

Furlotte, Nicholas A. ^{[21
]}

Joshi, Peter K. ^{[19
,22
]}

Kemper, Kathryn E. ^{[10
]}

Kleinman, Aaron ^{[21
]}

Langenberg, Claudia ^{[20
]}

Magi, Reedik ^{[11
]}

Trampush, Joey W. ^{[23
,24
]}

Verma, Shefali Setia ^{[25
]}

Wu, Yang ^{[10
]}

Lam, Max ^{[26
,27
]}

Zhao, Jing Hua ^{[20
]}

Zheng, Zhili ^{[10
,28
]}

Boardman, Jason D. ^{[2
,3
,4
]}

Campbell, Harry ^{[19
]}

Freese, Jeremy ^{[29
]}

Harris, Kathleen Mullan ^{[30
,31
]}

Hayward, Caroline ^{[32
]}

Herd, Pamela ^{[18
,33
]}

Kumari, Meena ^{[18
]}

Lencz, Todd ^{[34
,35
,36
,37
]}

Luan, Jian'an ^{[20
]}

Malhotra, Anil K. ^{[34
,35
,36
,37
]}

Metspalu, Andres ^{[11
,38
]}

Milani, Lili ^{[11
]}

Ong, Ken K. ^{[20
]}

Perry, John R. B. ^{[20
]}

机构：

[1] Univ Minnesota Twin Cities, Dept Psychol, Minneapolis, MN USA

[2] Univ Colorado, Dept Sociol, Boulder, CO 80309 USA

[3] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA

[4] Univ Colorado, Inst Behav Sci, Boulder, CO 80309 USA

[5] Vrije Univ Amsterdam, Dept Complex Trait Genet, Ctr Neurogen & Cognit Res, Amsterdam, Netherlands

[6] Vrije Univ Amsterdam, Sch Business & Econ, Dept Econ, Amsterdam, Netherlands

[7] Harvard Univ, Dept Econ, Cambridge, MA 02138 USA

[8] Harvard Univ, Dept Sociol, Cambridge, MA 02138 USA

[9] Univ Southern Calif, Ctr Econ & Social Res, Los Angeles, CA USA

[10] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia

[11] Univ Tartu, Estonian Genome Ctr, Tartu, Estonia

[12] Erasmus Univ, Inst Behav & Biol, Rotterdam, Netherlands

[13] Hosp Special Surg, Ctr Adv Value Musculoskeletal Care, 535 E 70th St, New York, NY 10021 USA

[14] Univ Copenhagen, Fac Hlth & Med Sci, Sect Metab Genet, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark

[15] Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark

[16] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[17] MIT & Harvard, Stanley Ctr Psychiat Res, Broad Inst, Cambridge, MA USA

[18] Univ Essex, Inst Social & Econ Res, Colchester, Essex, England

[19] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland

[20] Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England

[21] 23&Me Inc, Mountain View, CA USA

[22] Univ Lausanne Hosp, Inst Social & Prevent Med, Lausanne, Switzerland

[23] BrainWorkup LLC, Santa Monica, CA USA

[24] Univ Southern Calif, Keck Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA USA

[25] Geisinger Hlth Syst, Dept Biomed & Translat Informat, Danville, PA USA

[26] Inst Mental Hlth, Singapore, Singapore

[27] Genome Inst, Singapore, Singapore

[28] Wenzhou Med Univ, Sch Ophthalmol & Optometry, Eye Hosp, Wenzhou, Peoples R China

[29] Stanford Univ, Dept Sociol, Stanford, CA 94305 USA

[30] Univ North Carolina Chapel Hill, Dept Sociol, Chapel Hill, NC USA

[31] Univ North Carolina Chapel Hill, Carolina Populat Ctr, Chapel Hill, NC USA

[32] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland

[33] Univ Wisconsin, La Follette Sch Publ Affairs, Madison, WI USA

[34] Hofstra Northwell Sch Med, Dept Psychiat, Hempstead, NY USA

[35] Hofstra Northwell Sch Med, Dept Mol Med, Hempstead, NY USA

[36] Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY USA

[37] Zucker Hillside Hosp, Psychiat Res, Glen Oaks, CA USA

[38] Univ Tartu, Inst Mol & Cell Biol, Tartu, Estonia

[39] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland

[40] Univ Dundee, Div Populat Hlth Sci, Ninewells Hosp, Dundee, Scotland

[41] Univ Dundee, Med Sch, Dundee, Scotland

[42] Univ Dundee, Med Res Inst, Dundee, Scotland

[43] Univ Toronto, Dept Econ, Toronto, ON, Canada

[44] Princeton Univ, Dept Sociol, Princeton, NJ 08544 USA

[45] Queens Univ, Sch Policy Studies, Kingston, ON, Canada

[46] New York Univ Shanghai, Dept Econ, Shanghai, Peoples R China

[47] Natl Bur Econ Res, Cambridge, MA 02138 USA

[48] Karolinska Inst, Depnt Med Epidemiol & Biostat, Stockholm, Sweden

[49] Uppsala Univ, Dept Govt, Uppsala, Sweden

[50] Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland

来源：

NATURE GENETICS | 2018年 / 50卷 / 08期

基金：

瑞典研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

MAPPING CAUSAL VARIANTS; HERITABILITY; METAANALYSIS; LOCI; GWAS; BRAIN;

D O I：

10.1038/s41588-018-0147-3

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1112 / +

页数：16

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