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 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 journalArticle

    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 languageEnglish (US)
    Pages (from-to)1975-1986
    Number of pages12
    JournalPsychological Science
    Volume25
    Issue number11
    DOIs
    StatePublished - Nov 20 2014

    Fingerprint

    Genome-Wide Association Study
    Single Nucleotide Polymorphism
    Genome
    Genes

    Keywords

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

    ASJC Scopus subject areas

    • Psychology(all)

    Cite this

    Rietveld, C. A., Conley, D., Eriksson, N., Esko, T., Medland, S. E., Vinkhuyzen, A. A. E., ... 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

    Replicability and Robustness of Genome-Wide-Association Studies for Behavioral Traits. / Rietveld, Cornelius A.; Conley, Dalton; Eriksson, Nicholas; Esko, Tõnu; Medland, Sarah E.; Vinkhuyzen, Anna A E; Yang, Jian; Boardman, Jason D.; Chabris, Christopher F.; Dawes, Christopher; Domingue, Benjamin W.; Hinds, David A.; Johannesson, Magnus; Kiefer, Amy K.; Laibson, David; Magnusson, Patrik K E; Mountain, Joanna L.; Oskarsson, Sven; Rostapshova, Olga; Teumer, Alexander; Tung, Joyce Y.; Visscher, Peter M.; Benjamin, Daniel J.; Cesarini, David; Koellinger, Philipp D.

    In: Psychological Science, Vol. 25, No. 11, 20.11.2014, p. 1975-1986.

    Research output: Contribution to journalArticle

    Rietveld, CA, Conley, D, Eriksson, N, Esko, T, Medland, SE, Vinkhuyzen, AAE, Yang, J, Boardman, JD, Chabris, CF, Dawes, C, 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
    Rietveld CA, Conley D, Eriksson N, Esko T, Medland SE, Vinkhuyzen AAE et al. Replicability and Robustness of Genome-Wide-Association Studies for Behavioral Traits. Psychological Science. 2014 Nov 20;25(11):1975-1986. https://doi.org/10.1177/0956797614545132
    Rietveld, Cornelius A. ; Conley, Dalton ; Eriksson, Nicholas ; Esko, Tõnu ; Medland, Sarah E. ; Vinkhuyzen, Anna A E ; Yang, Jian ; Boardman, Jason D. ; Chabris, Christopher F. ; Dawes, Christopher ; Domingue, Benjamin W. ; Hinds, David A. ; Johannesson, Magnus ; Kiefer, Amy K. ; Laibson, David ; Magnusson, Patrik K E ; Mountain, Joanna L. ; Oskarsson, Sven ; Rostapshova, Olga ; Teumer, Alexander ; Tung, Joyce Y. ; Visscher, Peter M. ; Benjamin, Daniel J. ; Cesarini, David ; Koellinger, Philipp D. / Replicability and Robustness of Genome-Wide-Association Studies for Behavioral Traits. In: Psychological Science. 2014 ; Vol. 25, No. 11. pp. 1975-1986.
    @article{d3dd58093bb9410dab97ce2cbc1660f6,
    title = "Replicability and Robustness of Genome-Wide-Association Studies for Behavioral Traits",
    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.",
    keywords = "behavior genetics, educational attainment, genome-wide association study, individual differences, population stratification",
    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 Christopher Dawes 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.}",
    year = "2014",
    month = "11",
    day = "20",
    doi = "10.1177/0956797614545132",
    language = "English (US)",
    volume = "25",
    pages = "1975--1986",
    journal = "Psychological Science",
    issn = "0956-7976",
    publisher = "SAGE Publications Inc.",
    number = "11",

    }

    TY - JOUR

    T1 - Replicability and Robustness of Genome-Wide-Association Studies for Behavioral Traits

    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

    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

    Y1 - 2014/11/20

    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.

    KW - behavior genetics

    KW - educational attainment

    KW - genome-wide association study

    KW - individual differences

    KW - population stratification

    UR - http://www.scopus.com/inward/record.url?scp=84910659663&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84910659663&partnerID=8YFLogxK

    U2 - 10.1177/0956797614545132

    DO - 10.1177/0956797614545132

    M3 - Article

    C2 - 25287667

    AN - SCOPUS:84910659663

    VL - 25

    SP - 1975

    EP - 1986

    JO - Psychological Science

    JF - Psychological Science

    SN - 0956-7976

    IS - 11

    ER -