Replicability and Robustness of Genome-Wide-Association Studies for Behavioral Traits

被引：75

作者：

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

Conley, Dalton ^{[3
]}

Eriksson, Nicholas ^{[4
]}

Esko, Tonu ^{[5
]}

Medland, Sarah E. ^{[6
]}

Vinkhuyzen, Anna A. E. ^{[7
]}

Yang, Jian ^{[7
]}

Boardman, Jason D. ^{[8
,9
]}

Chabris, Christopher F. ^{[10
]}

Dawes, Christopher T. ^{[11
]}

Domingue, Benjamin W. ^{[8
]}

Hinds, David A. ^{[4
]}

Johannesson, Magnus ^{[12
]}

Kiefer, Amy K. ^{[4
]}

Laibson, David ^{[13
]}

Magnusson, Patrik K. E. ^{[14
]}

Mountain, Joanna L. ^{[4
]}

Oskarsson, Sven ^{[15
]}

Rostapshova, Olga ^{[13
]}

Teumer, Alexander ^{[16
]}

Tung, Joyce Y. ^{[4
]}

Visscher, Peter M. ^{[7
,17
]}

Benjamin, Daniel J. ^{[18
]}

Cesarini, David ^{[19
,20
]}

Koellinger, Philipp D. ^{[1
,2
,21
]}

机构：

[1] Erasmus Univ, Erasmus Sch Econ, Dept Appl Econ, Rotterdam, Netherlands

[2] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[3] NYU, Dept Sociol, New York, NY 10003 USA

[4] 23andMe Inc, Mountain View, CA USA

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

[6] Berghofer Med Res Inst, Queensland Inst Med Res, Brisbane, Qld, Australia

[7] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

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

[9] Univ Colorado, Dept Sociol, Denver, CO 80202 USA

[10] Union Coll, Dept Psychol, Union, NJ USA

[11] NYU, Wilf Family Dept Polit, New York, NY 10003 USA

[12] Stockholm Sch Econ, Dept Econ, Stockholm, Sweden

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

[14] Karolinska Inst, Dept Med Epidemiol & Biostat, S-10401 Stockholm, Sweden

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

[16] Greifswald Med Sch, Interfac Inst Genet & Funct Genom, Dept Funct Genom, Greifswald, Germany

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

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

[19] NYU, Dept Econ, Ctr Expt Social Sci, New York, NY 10003 USA

[20] NYU, Inst Interdisciplinary Study Decis Making, New York, NY 10003 USA

[21] Univ Amsterdam, Fac Econ & Business, NL-1018 TV Amsterdam, Netherlands

来源：

PSYCHOLOGICAL SCIENCE | 2014年 / 25卷 / 11期

关键词：

behavior genetics; educational attainment; individual differences; genome-wide association study; population stratification; STRATIFICATION; GWAS; SELECTION;

D O I：

10.1177/0956797614545132

中图分类号：

B84 [心理学];

学科分类号：

04 ; 0402 ;

摘要：

A recent genome-wide-association study of educational attainment identified three single-nucleotide polymorphisms (SNPs) whose associations, despite their small effect sizes (each R-2 approximate to 0.02%), reached genome-wide significance (p < 5 x 10(-8)) in a large discovery sample and were replicated in an independent sample (p < .05). The study also reported associations between educational attainment and indices of SNPs called polygenic scores. In three studies, we evaluated the robustness of these findings. Study 1 showed that the associations with all three SNPs were replicated in another large (N = 34,428) independent sample. We also found that the scores remained predictive (R-2 approximate to 2%) in regressions with stringent controls for stratification (Study 2) and in new within-family analyses (Study 3). Our results show that large and therefore well-powered genome-wide-association studies can identify replicable genetic associations with behavioral traits. The small effect sizes of individual SNPs are likely to be a major contributing factor explaining the striking contrast between our results and the disappointing replication record of most candidate-gene studies.

引用

页码：1975 / 1986

页数：12

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