Meta-analysis of genome-wide association studies for personality

M. H.M. De Moor; P. T. Costa; A. Terracciano; R. F. Krueger; E. J.C. De Geus; T. Toshiko; B. W.J.H. Penninx; T. Esko; P. A.F. Madden; J. Derringer; N. Amin; G. Willemsen; J. J. Hottenga; M. A. Distel; M. Uda; S. Sanna; P. Spinhoven; C. A. Hartman; P. Sullivan; A. Realo; J. Allik; A. C. Heath; M. L. Pergadia; A. Agrawal; P. Lin; R. Grucza; T. Nutile; M. Ciullo; D. Rujescu; I. Giegling; B. Konte; E. Widen; D. L. Cousminer; J. G. Eriksson; A. Palotie; L. Peltonen; M. Luciano; A. Tenesa; G. Davies; L. M. Lopez; N. K. Hansell; S. E. Medland; L. Ferrucci; D. Schlessinger; G. W. Montgomery; M. J. Wright; Y. S. Aulchenko; A. C.J.W. Janssens; B. A. Oostra; A. Metspalu; G. R. Abecasis; I. J. Deary; K. Räikkönen; L. J. Bierut; N. G. Martin; C. M. Van Duijn; D. I. Boomsma

doi:10.1038/mp.2010.128

Meta-analysis of genome-wide association studies for personality

M. H.M. De Moor^*
, P. T. Costa
, A. Terracciano
, R. F. Krueger
, E. J.C. De Geus
, T. Toshiko
, B. W.J.H. Penninx
, T. Esko
, P. A.F. Madden
, J. Derringer
, N. Amin
, G. Willemsen
, J. J. Hottenga
, M. A. Distel
, M. Uda
, S. Sanna
, P. Spinhoven
, C. A. Hartman
, P. Sullivan
, A. Realo

J. Allik, A. C. Heath, M. L. Pergadia, A. Agrawal, P. Lin, R. Grucza, T. Nutile, M. Ciullo, D. Rujescu, I. Giegling, B. Konte, E. Widen, D. L. Cousminer, J. G. Eriksson, A. Palotie, L. Peltonen, M. Luciano, A. Tenesa, G. Davies, L. M. Lopez, N. K. Hansell, S. E. Medland, L. Ferrucci, D. Schlessinger, G. W. Montgomery, M. J. Wright, Y. S. Aulchenko, A. C.J.W. Janssens, B. A. Oostra, A. Metspalu, G. R. Abecasis, I. J. Deary, K. Räikkönen, L. J. Bierut, N. G. Martin, C. M. Van Duijn, D. I. Boomsma

^*Corresponding author for this work

Department of Biological Psychology
Vrije Universiteit Amsterdam
National Institutes of Health
Department of Psychology
University of Minnesota Twin Cities
Interdisciplinary Center Psychopathology and Emotion regulation (ICPE)
University of Groningen
Departments of Clinical Psychology and Psychiatry
Leiden University
Department of Psychiatry
University of Amsterdam
Institute of Molecular and Cell Biology
University of Tartu
University of Tartu
Department of Psychiatry
Washington University St. Louis
Department of Epidemiology
Erasmus University Rotterdam
Istituto di Neurogeneticae Neurofarmacologia
National Research Council of Italy
University of North Carolina at Chapel Hill
Department of Psychology
Ludwig Maximilian University of Munich
FIMM Institute for Molecular Medicine Finland
University of Helsinki
National Institute for Health and Welfare
Department of General Practice and Primary Health Care
Vaasa Hospital District
Unit of General Practice
Helsinki University Hospital
Folkhalsan
Wellcome Trust Sanger Institute
Broad Institute
Department of Medical Genetics
Department of Psychology
University of Edinburgh
NHS Lothian
Queensland Institute of Medical Research
Department of Clinical Genetics
Department of Biostatistics
University of Michigan, Ann Arbor
Department of Psychology

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

257 Citations (Scopus)

Abstract

Personality can be thought of as a set of characteristics that influence people's thoughts, feelings and behavior across a variety of settings. Variation in personality is predictive of many outcomes in life, including mental health. Here we report on a meta-analysis of genome-wide association (GWA) data for personality in 10 discovery samples (17 375 adults) and five in silico replication samples (3294 adults). All participants were of European ancestry. Personality scores for Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness were based on the NEO Five-Factor Inventory. Genotype data of ∼2.4M single-nucleotide polymorphisms (SNPs; directly typed and imputed using HapMap data) were available. In the discovery samples, classical association analyses were performed under an additive model followed by meta-analysis using the weighted inverse variance method. Results showed genome-wide significance for Openness to Experience near the RASA1 gene on 5q14.3 (rs1477268 and rs2032794, P2.8 × 10 ^-8 and 3.1 × 10 ^-8) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P4.9 × 10 ^-8). We further conducted a gene-based test that confirmed the association of KATNAL2 to Conscientiousness. In silico replication did not, however, show significant associations of the top SNPs with Openness and Conscientiousness, although the direction of effect of the KATNAL2 SNP on Conscientiousness was consistent in all replication samples. Larger scale GWA studies and alternative approaches are required for confirmation of KATNAL2 as a novel gene affecting Conscientiousness.

Original language	English
Pages (from-to)	337-349
Number of pages	13
Journal	Molecular Psychiatry
Volume	17
Issue number	3
DOIs	https://doi.org/10.1038/mp.2010.128
Publication status	Published - 21 Dec 2010
Externally published	Yes

Keywords

Five-Factor Model
genetic variants
genome-wide association
meta-analysis
personality

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10.1038/mp.2010.128

Cite this

De Moor, M. H. M., Costa, P. T., Terracciano, A., Krueger, R. F., De Geus, E. J. C., Toshiko, T., Penninx, B. W. J. H., Esko, T., Madden, P. A. F., Derringer, J., Amin, N., Willemsen, G., Hottenga, J. J., Distel, M. A., Uda, M., Sanna, S., Spinhoven, P., Hartman, C. A., Sullivan, P., ... Boomsma, D. I. (2010). Meta-analysis of genome-wide association studies for personality. Molecular Psychiatry, 17(3), 337-349. https://doi.org/10.1038/mp.2010.128

@article{253742f1643547f9987f64153c6378e4,

title = "Meta-analysis of genome-wide association studies for personality",

abstract = "Personality can be thought of as a set of characteristics that influence people's thoughts, feelings and behavior across a variety of settings. Variation in personality is predictive of many outcomes in life, including mental health. Here we report on a meta-analysis of genome-wide association (GWA) data for personality in 10 discovery samples (17 375 adults) and five in silico replication samples (3294 adults). All participants were of European ancestry. Personality scores for Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness were based on the NEO Five-Factor Inventory. Genotype data of ∼2.4M single-nucleotide polymorphisms (SNPs; directly typed and imputed using HapMap data) were available. In the discovery samples, classical association analyses were performed under an additive model followed by meta-analysis using the weighted inverse variance method. Results showed genome-wide significance for Openness to Experience near the RASA1 gene on 5q14.3 (rs1477268 and rs2032794, P2.8 {\texttimes} 10 -8 and 3.1 {\texttimes} 10 -8) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P4.9 {\texttimes} 10 -8). We further conducted a gene-based test that confirmed the association of KATNAL2 to Conscientiousness. In silico replication did not, however, show significant associations of the top SNPs with Openness and Conscientiousness, although the direction of effect of the KATNAL2 SNP on Conscientiousness was consistent in all replication samples. Larger scale GWA studies and alternative approaches are required for confirmation of KATNAL2 as a novel gene affecting Conscientiousness.",

keywords = "Five-Factor Model, genetic variants, genome-wide association, meta-analysis, personality",

author = "\{De Moor\}, \{M. H.M.\} and Costa, \{P. T.\} and A. Terracciano and Krueger, \{R. F.\} and \{De Geus\}, \{E. J.C.\} and T. Toshiko and Penninx, \{B. W.J.H.\} and T. Esko and Madden, \{P. A.F.\} and J. Derringer and N. Amin and G. Willemsen and Hottenga, \{J. J.\} and Distel, \{M. A.\} and M. Uda and S. Sanna and P. Spinhoven and Hartman, \{C. A.\} and P. Sullivan and A. Realo and J. Allik and Heath, \{A. C.\} and Pergadia, \{M. L.\} and A. Agrawal and P. Lin and R. Grucza and T. Nutile and M. Ciullo and D. Rujescu and I. Giegling and B. Konte and E. Widen and Cousminer, \{D. L.\} and Eriksson, \{J. G.\} and A. Palotie and L. Peltonen and M. Luciano and A. Tenesa and G. Davies and Lopez, \{L. M.\} and Hansell, \{N. K.\} and Medland, \{S. E.\} and L. Ferrucci and D. Schlessinger and Montgomery, \{G. W.\} and Wright, \{M. J.\} and Aulchenko, \{Y. S.\} and Janssens, \{A. C.J.W.\} and Oostra, \{B. A.\} and A. Metspalu and Abecasis, \{G. R.\} and Deary, \{I. J.\} and K. R{\"a}ikk{\"o}nen and Bierut, \{L. J.\} and Martin, \{N. G.\} and \{Van Duijn\}, \{C. M.\} and Boomsma, \{D. I.\}",

year = "2010",

month = dec,

day = "21",

doi = "10.1038/mp.2010.128",

language = "English",

volume = "17",

pages = "337--349",

journal = "Molecular Psychiatry",

issn = "1359-4184",

publisher = "Springer Nature",

number = "3",

}

De Moor, MHM, Costa, PT, Terracciano, A, Krueger, RF, De Geus, EJC, Toshiko, T, Penninx, BWJH, Esko, T, Madden, PAF, Derringer, J, Amin, N, Willemsen, G, Hottenga, JJ, Distel, MA, Uda, M, Sanna, S, Spinhoven, P, Hartman, CA, Sullivan, P, Realo, A, Allik, J, Heath, AC, Pergadia, ML, Agrawal, A, Lin, P, Grucza, R, Nutile, T, Ciullo, M, Rujescu, D, Giegling, I, Konte, B, Widen, E, Cousminer, DL, Eriksson, JG, Palotie, A, Peltonen, L, Luciano, M, Tenesa, A, Davies, G, Lopez, LM, Hansell, NK, Medland, SE, Ferrucci, L, Schlessinger, D, Montgomery, GW, Wright, MJ, Aulchenko, YS, Janssens, ACJW, Oostra, BA, Metspalu, A, Abecasis, GR, Deary, IJ, Räikkönen, K, Bierut, LJ, Martin, NG, Van Duijn, CM & Boomsma, DI 2010, 'Meta-analysis of genome-wide association studies for personality', Molecular Psychiatry, vol. 17, no. 3, pp. 337-349. https://doi.org/10.1038/mp.2010.128

TY - JOUR

T1 - Meta-analysis of genome-wide association studies for personality

AU - De Moor, M. H.M.

AU - Costa, P. T.

AU - Terracciano, A.

AU - Krueger, R. F.

AU - De Geus, E. J.C.

AU - Toshiko, T.

AU - Penninx, B. W.J.H.

AU - Esko, T.

AU - Madden, P. A.F.

AU - Derringer, J.

AU - Amin, N.

AU - Willemsen, G.

AU - Hottenga, J. J.

AU - Distel, M. A.

AU - Uda, M.

AU - Sanna, S.

AU - Spinhoven, P.

AU - Hartman, C. A.

AU - Sullivan, P.

AU - Realo, A.

AU - Allik, J.

AU - Heath, A. C.

AU - Pergadia, M. L.

AU - Agrawal, A.

AU - Lin, P.

AU - Grucza, R.

AU - Nutile, T.

AU - Ciullo, M.

AU - Rujescu, D.

AU - Giegling, I.

AU - Konte, B.

AU - Widen, E.

AU - Cousminer, D. L.

AU - Eriksson, J. G.

AU - Palotie, A.

AU - Peltonen, L.

AU - Luciano, M.

AU - Tenesa, A.

AU - Davies, G.

AU - Lopez, L. M.

AU - Hansell, N. K.

AU - Medland, S. E.

AU - Ferrucci, L.

AU - Schlessinger, D.

AU - Montgomery, G. W.

AU - Wright, M. J.

AU - Aulchenko, Y. S.

AU - Janssens, A. C.J.W.

AU - Oostra, B. A.

AU - Metspalu, A.

AU - Abecasis, G. R.

AU - Deary, I. J.

AU - Räikkönen, K.

AU - Bierut, L. J.

AU - Martin, N. G.

AU - Van Duijn, C. M.

AU - Boomsma, D. I.

PY - 2010/12/21

Y1 - 2010/12/21

N2 - Personality can be thought of as a set of characteristics that influence people's thoughts, feelings and behavior across a variety of settings. Variation in personality is predictive of many outcomes in life, including mental health. Here we report on a meta-analysis of genome-wide association (GWA) data for personality in 10 discovery samples (17 375 adults) and five in silico replication samples (3294 adults). All participants were of European ancestry. Personality scores for Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness were based on the NEO Five-Factor Inventory. Genotype data of ∼2.4M single-nucleotide polymorphisms (SNPs; directly typed and imputed using HapMap data) were available. In the discovery samples, classical association analyses were performed under an additive model followed by meta-analysis using the weighted inverse variance method. Results showed genome-wide significance for Openness to Experience near the RASA1 gene on 5q14.3 (rs1477268 and rs2032794, P2.8 × 10 -8 and 3.1 × 10 -8) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P4.9 × 10 -8). We further conducted a gene-based test that confirmed the association of KATNAL2 to Conscientiousness. In silico replication did not, however, show significant associations of the top SNPs with Openness and Conscientiousness, although the direction of effect of the KATNAL2 SNP on Conscientiousness was consistent in all replication samples. Larger scale GWA studies and alternative approaches are required for confirmation of KATNAL2 as a novel gene affecting Conscientiousness.

AB - Personality can be thought of as a set of characteristics that influence people's thoughts, feelings and behavior across a variety of settings. Variation in personality is predictive of many outcomes in life, including mental health. Here we report on a meta-analysis of genome-wide association (GWA) data for personality in 10 discovery samples (17 375 adults) and five in silico replication samples (3294 adults). All participants were of European ancestry. Personality scores for Neuroticism, Extraversion, Openness to Experience, Agreeableness and Conscientiousness were based on the NEO Five-Factor Inventory. Genotype data of ∼2.4M single-nucleotide polymorphisms (SNPs; directly typed and imputed using HapMap data) were available. In the discovery samples, classical association analyses were performed under an additive model followed by meta-analysis using the weighted inverse variance method. Results showed genome-wide significance for Openness to Experience near the RASA1 gene on 5q14.3 (rs1477268 and rs2032794, P2.8 × 10 -8 and 3.1 × 10 -8) and for Conscientiousness in the brain-expressed KATNAL2 gene on 18q21.1 (rs2576037, P4.9 × 10 -8). We further conducted a gene-based test that confirmed the association of KATNAL2 to Conscientiousness. In silico replication did not, however, show significant associations of the top SNPs with Openness and Conscientiousness, although the direction of effect of the KATNAL2 SNP on Conscientiousness was consistent in all replication samples. Larger scale GWA studies and alternative approaches are required for confirmation of KATNAL2 as a novel gene affecting Conscientiousness.

KW - Five-Factor Model

KW - genetic variants

KW - genome-wide association

KW - meta-analysis

KW - personality

UR - https://www.scopus.com/pages/publications/84857356586

U2 - 10.1038/mp.2010.128

DO - 10.1038/mp.2010.128

M3 - Article

C2 - 21173776

AN - SCOPUS:84857356586

SN - 1359-4184

VL - 17

SP - 337

EP - 349

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 3

ER -

Meta-analysis of genome-wide association studies for personality

Abstract

Keywords

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