Common genetic variants associated with cognitive performance identified using the proxy-phenotype method

被引：173

作者：

Rietveld, Cornelius A. ^{[1
,2
]}

Esko, Tonu ^{[7
,8
,9
,10
]}

Davies, Gail ^{[11
,12
]}

Pers, Tune H. ^{[7
,8
]}

Turley, Patrick ^{[14
]}

Benyamin, Beben ^{[16
]}

Chabris, Christopher F. ^{[17
]}

Emilsson, Valur ^{[18
,19
]}

Johnson, Andrew D. ^{[20
]}

Lee, James J. ^{[15
,21
]}

de Leeuw, Christiaan ^{[22
,23
,24
]}

Marioni, Riccardo E. ^{[11
,16
,25
]}

Medland, Sarah E. ^{[27
]}

Miller, Michael B. ^{[21
]}

Rostapshova, Olga ^{[29
]}

van der Lee, Sven J. ^{[5
]}

Vinkhuyzen, Anna A. E. ^{[16
]}

Amin, Najaf ^{[5
]}

Conley, Dalton ^{[30
]}

Derringer, Jaime ^{[32
]}

van Duijn, Cornelia M. ^{[5
,33
]}

Fehrmann, Rudolf ^{[34
]}

Franke, Lude ^{[34
]}

Glaeser, Edward L. ^{[14
]}

Hansell, Narelle K. ^{[35
]}

Hayward, Caroline ^{[25
,26
]}

Iacono, William G. ^{[21
]}

Ibrahim-Verbaas, Carla ^{[3
,29
]}

Jaddoe, Vincent ^{[2
,6
]}

Karjalainen, Juha ^{[34
]}

Laibson, David ^{[14
]}

Lichtenstein, Paul ^{[14
]}

Liewald, David C. ^{[11
]}

Magnusson, Patrik K. E. ^{[36
]}

Martin, Nicholas G. ^{[28
]}

McGue, Matt ^{[21
]}

McMahon, George ^{[37
]}

Pedersen, Nancy L. ^{[36
]}

Pinker, Steven ^{[15
]}

Porteous, David J. ^{[11
,25
]}

Posthuma, Danielle ^{[22
,23
,38
,39
]}

Rivadeneira, Fernando ^{[2
,4
]}

Smith, Blair H. ^{[40
]}

Starr, John M. ^{[11
,13
]}

Tiemeier, Henning ^{[2
,38
]}

Timpson, Nicholas J. ^{[41
]}

Trzaskowski, Maciej ^{[42
]}

Uitterlinden, Andre G. ^{[2
,4
]}

Verhulst, Frank C. ^{[38
]}

Ward, Mary E. ^{[37
]}

机构：

[1] Erasmus Univ, Erasmus Sch Econ, Dept Appl Econ, NL-3000 DR Rotterdam, Netherlands

[2] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands

[3] Erasmus MC, Dept Neurol, NL-3000 CA Rotterdam, Netherlands

[4] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands

[5] Erasmus MC, Dept Epidemiol & Biostat, Genet Epidemiol Unit, NL-3000 CA Rotterdam, Netherlands

[6] Erasmus MC, Generat Study Grp R, NL-3000 CA Rotterdam, Netherlands

[7] Boston Childrens Hosp, Div Genet & Endocrinol, Boston, MA 02115 USA

[8] Broad Inst Massachusetts Inst Technol & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA

[9] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[10] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia

[11] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland

[12] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland

[13] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland

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

[15] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA

[16] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia

[17] Union Coll, Dept Psychol, Schenectady, NY 12308 USA

[18] Iceland Heart Assoc, IS-201 Kopavogur, Iceland

[19] Univ Iceland, Fac Pharmaceut Sci, IS-107 Reykjavik, Iceland

[20] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA

[21] Univ Minnesota, Dept Psychol, Minneapolis, MN 55455 USA

[22] Vrije Univ Amsterdam, Dept Complex Trait Genet, NL-1081 HV Amsterdam, Netherlands

[23] Vrije Univ Amsterdam Med Ctr, NL-1081 HV Amsterdam, Netherlands

[24] Radboud Univ Nijmegen, Fac Sci, Inst Comp & Informat Sci, Machine Learning Grp, NL-6500 GL Nijmegen, Netherlands

[25] Univ Edinburgh, Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland

[26] Univ Edinburgh, Inst Genet & Mol Med, Human Genet Unit, MRC, Edinburgh EH4 2XU, Midlothian, Scotland

[27] QIMR Berghofer Med Res Inst, Quantitat Genet Lab, Brisbane, Qld 4029, Australia

[28] QIMR Berghofer Med Res Inst, Genet Epidemiol Lab, Brisbane, Qld 4029, Australia

[29] Harvard Univ, Kennedy Sch, Cambridge, MA 02139 USA

[30] NYU, Dept Sociol, New York, NY 10012 USA

[31] NYU, Dept Econ, Ctr Expt Social Sci, New York, NY 10012 USA

[32] Univ Illinois, Dept Psychol, Urbana, IL 61820 USA

[33] Leiden Univ, Med Ctr, Ctr Med Syst Biol, NL-2300 RC Leiden, Netherlands

[34] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9713 GZ Groningen, Netherlands

[35] QIMR Berghofer Med Res Inst, Neuroimaging Genet Grp, Brisbane, Qld 4029, Australia

[36] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden

[37] Univ Bristol, Sch Social & Community Med, Bristol BS8 2PR, Avon, England

[38] Erasmus MC, Dept Child & Adolescent Psychiat, NL-3000 CB Rotterdam, Netherlands

[39] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, NL-1081 BT Amsterdam, Netherlands

[40] Univ Dundee, Med Res Inst, Dundee DD2 4RB, Scotland

[41] Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol BS8 2PR, Avon, England

[42] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, MRC, London SE5 8AF, England

[43] Stockholm Sch Econ, Dept Econ, S-11383 Stockholm, Sweden

[44] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst, Brisbane, Qld 4102, Australia

[45] Cornell Univ, Dept Econ, Ithaca, NY 14853 USA

[46] NYU, Inst Interdisciplinary Study Decis Making, New York, NY 10012 USA

[47] Univ Amsterdam, Fac Econ & Business, NL-1012 WX Amsterdam, Netherlands

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2014年 / 111卷 / 38期

基金：

美国国家卫生研究院; 瑞典研究理事会; 美国国家科学基金会; 英国生物技术与生命科学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; ACADEMIC-ACHIEVEMENT; INTELLIGENCE; LOCI; COMPONENTS; GWAS;

D O I：

10.1073/pnas.1404623111

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxy-phenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education-associated SNPs. Second, using independent samples (n = 24,189), we measure the association of these education-associated SNPs with cognitive performance. Three SNPs (rs1487441, rs7923609, and rs2721173) are significantly associated with cognitive performance after correction for multiple hypothesis testing. In an independent sample of older Americans (n = 8,652), we also show that a polygenic score derived from the education-associated SNPs is associated with memory and absence of dementia. Convergent evidence from a set of bioinformatics analyses implicates four specific genes (KNCMA1, NRXN1, POU2F3, and SCRT). All of these genes are associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory.

引用

页码：13790 / 13794

页数：5

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