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

Cornelius A. Rietveld; Dalton Conley; Nicholas Eriksson; Tõnu Esko; Sarah E. Medland; Anna A.E. Vinkhuyzen; Jian Yang; Jason D. Boardman; Christopher F. Chabris; Christopher T. Dawes; Benjamin W. Domingue; David A. Hinds; Magnus Johannesson; Amy K. Kiefer; David Laibson; Patrik K.E. Magnusson; Joanna L. Mountain; Sven Oskarsson; Olga Rostapshova; Alexander Teumer; Joyce Y. Tung; Peter M. Visscher; Daniel J. Benjamin; David Cesarini; Philipp D. Koellinger

doi:10.1177/0956797614545132

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

Cornelius A. Rietveld, Dalton Conley, Nicholas Eriksson, Tõnu Esko, Sarah E. Medland, Anna A.E. Vinkhuyzen, Jian Yang, Jason D. Boardman, Christopher F. Chabris, Christopher T. Dawes, Benjamin W. Domingue, David A. Hinds, Magnus Johannesson, Amy K. Kiefer, David Laibson, Patrik K.E. Magnusson, Joanna L. Mountain, Sven Oskarsson, Olga Rostapshova, Alexander TeumerJoyce Y. Tung, Peter M. Visscher, Daniel J. Benjamin, David Cesarini, Philipp D. Koellinger

Research output: Contribution to journal › Article › peer-review

Abstract

A recent genome-wide-association study of educational attainment identified three single-nucleotide polymorphisms (SNPs) whose associations, despite their small effect sizes (each R2 ≈ 0.02%), reached genome-wide significance (p < 5 × 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 (R2 ≈ 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.

Original language	English (US)
Pages (from-to)	1975-1986
Number of pages	12
Journal	Psychological Science
Volume	25
Issue number	11
DOIs	https://doi.org/10.1177/0956797614545132
State	Published - Nov 20 2014

Keywords

behavior genetics
educational attainment
genome-wide association study
individual differences
population stratification

ASJC Scopus subject areas

General Psychology

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10.1177/0956797614545132

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Rietveld, C. A., Conley, D., Eriksson, N., Esko, T., Medland, S. E., Vinkhuyzen, A. A. E., Yang, J., Boardman, J. D., Chabris, C. F., Dawes, C. T., Domingue, B. W., Hinds, D. A., Johannesson, M., Kiefer, A. K., Laibson, D., Magnusson, P. K. E., Mountain, J. L., Oskarsson, S., Rostapshova, O., ... Koellinger, P. D. (2014). Replicability and Robustness of Genome-Wide-Association Studies for Behavioral Traits. Psychological Science, 25(11), 1975-1986. https://doi.org/10.1177/0956797614545132

Rietveld, CA, Conley, D, Eriksson, N, Esko, T, Medland, SE, Vinkhuyzen, AAE, Yang, J, Boardman, JD, Chabris, CF, Dawes, CT, Domingue, BW, Hinds, DA, Johannesson, M, Kiefer, AK, Laibson, D, Magnusson, PKE, Mountain, JL, Oskarsson, S, Rostapshova, O, Teumer, A, Tung, JY, Visscher, PM, Benjamin, DJ, Cesarini, D & Koellinger, PD 2014, 'Replicability and Robustness of Genome-Wide-Association Studies for Behavioral Traits', Psychological Science, vol. 25, no. 11, pp. 1975-1986. https://doi.org/10.1177/0956797614545132

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abstract = "A recent genome-wide-association study of educational attainment identified three single-nucleotide polymorphisms (SNPs) whose associations, despite their small effect sizes (each R2 ≈ 0.02%), reached genome-wide significance (p < 5 × 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 (R2 ≈ 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.",

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author = "Rietveld, {Cornelius A.} and Dalton Conley and Nicholas Eriksson and T{\~o}nu Esko and Medland, {Sarah E.} and Vinkhuyzen, {Anna A.E.} and Jian Yang and Boardman, {Jason D.} and Chabris, {Christopher F.} and Dawes, {Christopher T.} and Domingue, {Benjamin W.} and Hinds, {David A.} and Magnus Johannesson and Kiefer, {Amy K.} and David Laibson and Magnusson, {Patrik K.E.} and Mountain, {Joanna L.} and Sven Oskarsson and Olga Rostapshova and Alexander Teumer and Tung, {Joyce Y.} and Visscher, {Peter M.} and Benjamin, {Daniel J.} and David Cesarini and Koellinger, {Philipp D.}",

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AU - Rietveld, Cornelius A.

AU - Conley, Dalton

AU - Eriksson, Nicholas

AU - Esko, Tõnu

AU - Medland, Sarah E.

AU - Vinkhuyzen, Anna A.E.

AU - Yang, Jian

AU - Boardman, Jason D.

AU - Chabris, Christopher F.

AU - Dawes, Christopher T.

AU - Domingue, Benjamin W.

AU - Hinds, David A.

AU - Johannesson, Magnus

AU - Kiefer, Amy K.

AU - Laibson, David

AU - Magnusson, Patrik K.E.

AU - Mountain, Joanna L.

AU - Oskarsson, Sven

AU - Rostapshova, Olga

AU - Teumer, Alexander

AU - Tung, Joyce Y.

AU - Visscher, Peter M.

AU - Benjamin, Daniel J.

AU - Cesarini, David

AU - Koellinger, Philipp D.

PY - 2014/11/20

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N2 - A recent genome-wide-association study of educational attainment identified three single-nucleotide polymorphisms (SNPs) whose associations, despite their small effect sizes (each R2 ≈ 0.02%), reached genome-wide significance (p < 5 × 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 (R2 ≈ 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.

AB - A recent genome-wide-association study of educational attainment identified three single-nucleotide polymorphisms (SNPs) whose associations, despite their small effect sizes (each R2 ≈ 0.02%), reached genome-wide significance (p < 5 × 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 (R2 ≈ 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.

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

Abstract

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