Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

S.M. van den Berg; M.H.M. de Moor; C.J.H. Verweij; R.F. Krueger; M. Luciano; A.A. Vasquez; L.K. Matteson; J. Derringer; T. Esko; N. Amin; S.D. Gordon; N.K. Hansell; A.B. Hart; I. Seppälä; J.E. Huffman; B. Konte; J. Lahti; M. Miller; T. Nutile; T. Tanaka; A. Teumer; A. Viktorin; J. Wedenoja; A. Abdellaoui; G.R. Abecasis; D.E. Adkins; A. Agrawal; J. Allik; K. Appel; T.B. Bigdeli; F. Busonero; H. Campbell; P.T. Costa; G. Davey Smith; G. Davies; H. de Wit; J. Ding; B.E. Engelhardt; J.G. Eriksson; I.O. Fedko; L. Ferrucci; B. Franke; I. Giegling; R. Grucza; A.M. Hartmann; A.C. Heath; K. Heinonen; A.K. Henders; G. Homuth; J.J. Hottenga; W.G. Iacono; J. Janzing; M Jokela; R. Karlsson; J.P. Kemp; M.G. Kirkpatrick; A. Latvala; T. Lehtimäki; D.C. Liewald; P.A.F. Madden; C. Magri; P.K.E. Magnusson; J. Marten; A. Maschio; H. Mbarek; S.E. Medland; E. Mihailov; Y. Milaneschi; G.W. Montgomery; M. Nauck; M.G. Nivard; K.G. Ouwens; A. Palotie; E. Pettersson; O. Polasek; Y. Qian; L. Pulkki-Raback; O.T. Raitakari; A. Realo; R.J. Rose; D. Ruggiero; C.O. Schmidt; W.S. Slutske; R. Sorice; J.M. Starr; B. St Pourcain; A.R. Sutin; N.J. Timpson; H. Trochet; L. Zgaga; D. Porteous; A. Minelli; A.A. Palmer; D. Rujescu; M. Ciullo; C. Hayward; I. Rudan; A. Metspalu; J. Kaprio; I.J. Deary; K. Räikkönen; J.F. Wilson; L. Keltikangas-Järvinen; L.J. Bierut; J.M. Hettema; H.J. Grabe; B.W.J.H. Penninx; C.M. van Duijn; D.M. Evans; D. Schlessinger; N.L. Pedersen; A. Terracciano; M. McGue; N.G. Martin; D.I. Boomsma

doi:10.1007/s10519-015-9735-5

Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

S.M. van den Berg, M.H.M. de Moor, C.J.H. Verweij, R.F. Krueger, M. Luciano, A.A. Vasquez, L.K. Matteson, J. Derringer, T. Esko, N. Amin, S.D. Gordon, N.K. Hansell, A.B. Hart, I. Seppälä, J.E. Huffman, B. Konte, J. Lahti, M. Miller, T. Nutile, T. TanakaA. Teumer, A. Viktorin, J. Wedenoja, A. Abdellaoui, G.R. Abecasis, D.E. Adkins, A. Agrawal, J. Allik, K. Appel, T.B. Bigdeli, F. Busonero, H. Campbell, P.T. Costa, G. Davey Smith, G. Davies, H. de Wit, J. Ding, B.E. Engelhardt, J.G. Eriksson, I.O. Fedko, L. Ferrucci, B. Franke, I. Giegling, R. Grucza, A.M. Hartmann, A.C. Heath, K. Heinonen, A.K. Henders, G. Homuth, J.J. Hottenga, W.G. Iacono, J. Janzing, M Jokela, R. Karlsson, J.P. Kemp, M.G. Kirkpatrick, A. Latvala, T. Lehtimäki, D.C. Liewald, P.A.F. Madden, C. Magri, P.K.E. Magnusson, J. Marten, A. Maschio, H. Mbarek, S.E. Medland, E. Mihailov, Y. Milaneschi, G.W. Montgomery, M. Nauck, M.G. Nivard, K.G. Ouwens, A. Palotie, E. Pettersson, O. Polasek, Y. Qian, L. Pulkki-Raback, O.T. Raitakari, A. Realo, R.J. Rose, D. Ruggiero, C.O. Schmidt, W.S. Slutske, R. Sorice, J.M. Starr, B. St Pourcain, A.R. Sutin, N.J. Timpson, H. Trochet, L. Zgaga, D. Porteous, A. Minelli, A.A. Palmer, D. Rujescu, M. Ciullo, C. Hayward, I. Rudan, A. Metspalu, J. Kaprio, I.J. Deary, K. Räikkönen, J.F. Wilson, L. Keltikangas-Järvinen, L.J. Bierut, J.M. Hettema, H.J. Grabe, B.W.J.H. Penninx, C.M. van Duijn, D.M. Evans, D. Schlessinger, N.L. Pedersen, A. Terracciano, M. McGue, N.G. Martin, D.I. Boomsma

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Abstract

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

Original language	English
Pages (from-to)	170-182
Journal	Behavior Genetics
Volume	46
Issue number	2
DOIs	https://doi.org/10.1007/s10519-015-9735-5
Publication status	Published - 2016

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van den Berg, S. M., de Moor, M. H. M., Verweij, C. J. H., Krueger, R. F., Luciano, M., Vasquez, A. A., Matteson, L. K., Derringer, J., Esko, T., Amin, N., Gordon, S. D., Hansell, N. K., Hart, A. B., Seppälä, I., Huffman, J. E., Konte, B., Lahti, J., Miller, M., Nutile, T., ... Boomsma, D. I. (2016). Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium. Behavior Genetics, 46(2), 170-182. https://doi.org/10.1007/s10519-015-9735-5

@article{d7a522f34d8840939abb6a5cdc9d5c02,

title = "Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium",

abstract = "Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.",

author = "{van den Berg}, S.M. and {de Moor}, M.H.M. and C.J.H. Verweij and R.F. Krueger and M. Luciano and A.A. Vasquez and L.K. Matteson and J. Derringer and T. Esko and N. Amin and S.D. Gordon and N.K. Hansell and A.B. Hart and I. Sepp{\"a}l{\"a} and J.E. Huffman and B. Konte and J. Lahti and M. Miller and T. Nutile and T. Tanaka and A. Teumer and A. Viktorin and J. Wedenoja and A. Abdellaoui and G.R. Abecasis and D.E. Adkins and A. Agrawal and J. Allik and K. Appel and T.B. Bigdeli and F. Busonero and H. Campbell and P.T. Costa and {Davey Smith}, G. and G. Davies and {de Wit}, H. and J. Ding and B.E. Engelhardt and J.G. Eriksson and I.O. Fedko and L. Ferrucci and B. Franke and I. Giegling and R. Grucza and A.M. Hartmann and A.C. Heath and K. Heinonen and A.K. Henders and G. Homuth and J.J. Hottenga and W.G. Iacono and J. Janzing and M Jokela and R. Karlsson and J.P. Kemp and M.G. Kirkpatrick and A. Latvala and T. Lehtim{\"a}ki and D.C. Liewald and P.A.F. Madden and C. Magri and P.K.E. Magnusson and J. Marten and A. Maschio and H. Mbarek and S.E. Medland and E. Mihailov and Y. Milaneschi and G.W. Montgomery and M. Nauck and M.G. Nivard and K.G. Ouwens and A. Palotie and E. Pettersson and O. Polasek and Y. Qian and L. Pulkki-Raback and O.T. Raitakari and A. Realo and R.J. Rose and D. Ruggiero and C.O. Schmidt and W.S. Slutske and R. Sorice and J.M. Starr and {St Pourcain}, B. and A.R. Sutin and N.J. Timpson and H. Trochet and L. Zgaga and D. Porteous and A. Minelli and A.A. Palmer and D. Rujescu and M. Ciullo and C. Hayward and I. Rudan and A. Metspalu and J. Kaprio and I.J. Deary and K. R{\"a}ikk{\"o}nen and J.F. Wilson and L. Keltikangas-J{\"a}rvinen and L.J. Bierut and J.M. Hettema and H.J. Grabe and B.W.J.H. Penninx and {van Duijn}, C.M. and D.M. Evans and D. Schlessinger and N.L. Pedersen and A. Terracciano and M. McGue and N.G. Martin and D.I. Boomsma",

year = "2016",

doi = "10.1007/s10519-015-9735-5",

language = "English",

volume = "46",

pages = "170--182",

journal = "Behavior Genetics",

issn = "0001-8244",

publisher = "Springer",

number = "2",

}

van den Berg, SM, de Moor, MHM, Verweij, CJH, Krueger, RF, Luciano, M, Vasquez, AA, Matteson, LK, Derringer, J, Esko, T, Amin, N, Gordon, SD, Hansell, NK, Hart, AB, Seppälä, I, Huffman, JE, Konte, B, Lahti, J, Miller, M, Nutile, T, Tanaka, T, Teumer, A, Viktorin, A, Wedenoja, J, Abdellaoui, A, Abecasis, GR, Adkins, DE, Agrawal, A, Allik, J, Appel, K, Bigdeli, TB, Busonero, F, Campbell, H, Costa, PT, Davey Smith, G, Davies, G, de Wit, H, Ding, J, Engelhardt, BE, Eriksson, JG, Fedko, IO, Ferrucci, L, Franke, B, Giegling, I, Grucza, R, Hartmann, AM, Heath, AC, Heinonen, K, Henders, AK, Homuth, G, Hottenga, JJ, Iacono, WG, Janzing, J, Jokela, M, Karlsson, R, Kemp, JP, Kirkpatrick, MG, Latvala, A, Lehtimäki, T, Liewald, DC, Madden, PAF, Magri, C, Magnusson, PKE, Marten, J, Maschio, A, Mbarek, H, Medland, SE, Mihailov, E, Milaneschi, Y, Montgomery, GW, Nauck, M, Nivard, MG, Ouwens, KG, Palotie, A, Pettersson, E, Polasek, O, Qian, Y, Pulkki-Raback, L, Raitakari, OT, Realo, A, Rose, RJ, Ruggiero, D, Schmidt, CO, Slutske, WS, Sorice, R, Starr, JM, St Pourcain, B, Sutin, AR, Timpson, NJ, Trochet, H, Zgaga, L, Porteous, D, Minelli, A, Palmer, AA, Rujescu, D, Ciullo, M, Hayward, C, Rudan, I, Metspalu, A, Kaprio, J, Deary, IJ, Räikkönen, K, Wilson, JF, Keltikangas-Järvinen, L, Bierut, LJ, Hettema, JM, Grabe, HJ, Penninx, BWJH, van Duijn, CM, Evans, DM, Schlessinger, D, Pedersen, NL, Terracciano, A, McGue, M, Martin, NG & Boomsma, DI 2016, 'Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium', Behavior Genetics, vol. 46, no. 2, pp. 170-182. https://doi.org/10.1007/s10519-015-9735-5

TY - JOUR

T1 - Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

AU - van den Berg, S.M.

AU - de Moor, M.H.M.

AU - Verweij, C.J.H.

AU - Krueger, R.F.

AU - Luciano, M.

AU - Vasquez, A.A.

AU - Matteson, L.K.

AU - Derringer, J.

AU - Esko, T.

AU - Amin, N.

AU - Gordon, S.D.

AU - Hansell, N.K.

AU - Hart, A.B.

AU - Seppälä, I.

AU - Huffman, J.E.

AU - Konte, B.

AU - Lahti, J.

AU - Miller, M.

AU - Nutile, T.

AU - Tanaka, T.

AU - Teumer, A.

AU - Viktorin, A.

AU - Wedenoja, J.

AU - Abdellaoui, A.

AU - Abecasis, G.R.

AU - Adkins, D.E.

AU - Agrawal, A.

AU - Allik, J.

AU - Appel, K.

AU - Bigdeli, T.B.

AU - Busonero, F.

AU - Campbell, H.

AU - Costa, P.T.

AU - Davey Smith, G.

AU - Davies, G.

AU - de Wit, H.

AU - Ding, J.

AU - Engelhardt, B.E.

AU - Eriksson, J.G.

AU - Fedko, I.O.

AU - Ferrucci, L.

AU - Franke, B.

AU - Giegling, I.

AU - Grucza, R.

AU - Hartmann, A.M.

AU - Heath, A.C.

AU - Heinonen, K.

AU - Henders, A.K.

AU - Homuth, G.

AU - Hottenga, J.J.

AU - Iacono, W.G.

AU - Janzing, J.

AU - Jokela, M

AU - Karlsson, R.

AU - Kemp, J.P.

AU - Kirkpatrick, M.G.

AU - Latvala, A.

AU - Lehtimäki, T.

AU - Liewald, D.C.

AU - Madden, P.A.F.

AU - Magri, C.

AU - Magnusson, P.K.E.

AU - Marten, J.

AU - Maschio, A.

AU - Mbarek, H.

AU - Medland, S.E.

AU - Mihailov, E.

AU - Milaneschi, Y.

AU - Montgomery, G.W.

AU - Nauck, M.

AU - Nivard, M.G.

AU - Ouwens, K.G.

AU - Palotie, A.

AU - Pettersson, E.

AU - Polasek, O.

AU - Qian, Y.

AU - Pulkki-Raback, L.

AU - Raitakari, O.T.

AU - Realo, A.

AU - Rose, R.J.

AU - Ruggiero, D.

AU - Schmidt, C.O.

AU - Slutske, W.S.

AU - Sorice, R.

AU - Starr, J.M.

AU - St Pourcain, B.

AU - Sutin, A.R.

AU - Timpson, N.J.

AU - Trochet, H.

AU - Zgaga, L.

AU - Porteous, D.

AU - Minelli, A.

AU - Palmer, A.A.

AU - Rujescu, D.

AU - Ciullo, M.

AU - Hayward, C.

AU - Rudan, I.

AU - Metspalu, A.

AU - Kaprio, J.

AU - Deary, I.J.

AU - Räikkönen, K.

AU - Wilson, J.F.

AU - Keltikangas-Järvinen, L.

AU - Bierut, L.J.

AU - Hettema, J.M.

AU - Grabe, H.J.

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

AU - van Duijn, C.M.

AU - Evans, D.M.

AU - Schlessinger, D.

AU - Pedersen, N.L.

AU - Terracciano, A.

AU - McGue, M.

AU - Martin, N.G.

AU - Boomsma, D.I.

PY - 2016

Y1 - 2016

N2 - Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

AB - Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion.

U2 - 10.1007/s10519-015-9735-5

DO - 10.1007/s10519-015-9735-5

M3 - Article

SN - 0001-8244

VL - 46

SP - 170

EP - 182

JO - Behavior Genetics

JF - Behavior Genetics

IS - 2

ER -

Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

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