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 & 95 others 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

Research output: Scientific - peer-reviewArticle

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 languageEnglish
Pages (from-to)170-182
JournalBehavior Genetics
Volume46
Issue number2
DOIs
StatePublished - 2016

Cite this

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.; Tanaka, T.; Teumer, A.; Viktorin, A.; Wedenoja, J.; Abdellaoui, A.; Abecasis, G.R.; Adkins, D.E.; Agrawal, A.; Allik, J.; Appel, K.; Bigdeli, T.B.; Busonero, F.; Campbell, H.; Costa, P.T.; Davey Smith, G.; Davies, G.; de Wit, H.; Ding, J.; Engelhardt, B.E.; Eriksson, J.G.; Fedko, I.O.; Ferrucci, L.; Franke, B.; Giegling, I.; Grucza, R.; Hartmann, A.M.; Heath, A.C.; Heinonen, K.; Henders, A.K.; Homuth, G.; Hottenga, J.J.; Iacono, W.G.; Janzing, J.; Jokela, M; Karlsson, R.; Kemp, J.P.; Kirkpatrick, M.G.; Latvala, A.; Lehtimäki, T.; Liewald, D.C.; Madden, P.A.F.; Magri, C.; Magnusson, P.K.E.; Marten, J.; Maschio, A.; Mbarek, H.; Medland, S.E.; Mihailov, E.; Milaneschi, Y.; Montgomery, G.W.; Nauck, M.; Nivard, M.G.; Ouwens, K.G.; Palotie, A.; Pettersson, E.; Polasek, O.; Qian, Y.; Pulkki-Raback, L.; Raitakari, O.T.; Realo, A.; Rose, R.J.; Ruggiero, D.; Schmidt, C.O.; Slutske, W.S.; Sorice, R.; Starr, J.M.; St Pourcain, B.; Sutin, A.R.; Timpson, N.J.; Trochet, H.; Zgaga, L.; Porteous, D.; Minelli, A.; Palmer, A.A.; Rujescu, D.; Ciullo, M.; Hayward, C.; Rudan, I.; Metspalu, A.; Kaprio, J.; Deary, I.J.; Räikkönen, K.; Wilson, J.F.; Keltikangas-Järvinen, L.; Bierut, L.J.; Hettema, J.M.; Grabe, H.J.; Penninx, B.W.J.H.; van Duijn, C.M.; Evans, D.M.; Schlessinger, D.; Pedersen, N.L.; Terracciano, A.; McGue, M.; Martin, N.G.; Boomsma, D.I. / Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium.

In: Behavior Genetics, Vol. 46, No. 2, 2016, p. 170-182.

Research output: Scientific - peer-reviewArticle

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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.",
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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. DOI: 10.1007/s10519-015-9735-5

Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium. / 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.; Tanaka, T.; Teumer, A.; Viktorin, A.; Wedenoja, J.; Abdellaoui, A.; Abecasis, G.R.; Adkins, D.E.; Agrawal, A.; Allik, J.; Appel, K.; Bigdeli, T.B.; Busonero, F.; Campbell, H.; Costa, P.T.; Davey Smith, G.; Davies, G.; de Wit, H.; Ding, J.; Engelhardt, B.E.; Eriksson, J.G.; Fedko, I.O.; Ferrucci, L.; Franke, B.; Giegling, I.; Grucza, R.; Hartmann, A.M.; Heath, A.C.; Heinonen, K.; Henders, A.K.; Homuth, G.; Hottenga, J.J.; Iacono, W.G.; Janzing, J.; Jokela, M; Karlsson, R.; Kemp, J.P.; Kirkpatrick, M.G.; Latvala, A.; Lehtimäki, T.; Liewald, D.C.; Madden, P.A.F.; Magri, C.; Magnusson, P.K.E.; Marten, J.; Maschio, A.; Mbarek, H.; Medland, S.E.; Mihailov, E.; Milaneschi, Y.; Montgomery, G.W.; Nauck, M.; Nivard, M.G.; Ouwens, K.G.; Palotie, A.; Pettersson, E.; Polasek, O.; Qian, Y.; Pulkki-Raback, L.; Raitakari, O.T.; Realo, A.; Rose, R.J.; Ruggiero, D.; Schmidt, C.O.; Slutske, W.S.; Sorice, R.; Starr, J.M.; St Pourcain, B.; Sutin, A.R.; Timpson, N.J.; Trochet, H.; Zgaga, L.; Porteous, D.; Minelli, A.; Palmer, A.A.; Rujescu, D.; Ciullo, M.; Hayward, C.; Rudan, I.; Metspalu, A.; Kaprio, J.; Deary, I.J.; Räikkönen, K.; Wilson, J.F.; Keltikangas-Järvinen, L.; Bierut, L.J.; Hettema, J.M.; Grabe, H.J.; Penninx, B.W.J.H.; van Duijn, C.M.; Evans, D.M.; Schlessinger, D.; Pedersen, N.L.; Terracciano, A.; McGue, M.; Martin, N.G.; Boomsma, D.I.

In: Behavior Genetics, Vol. 46, No. 2, 2016, p. 170-182.

Research output: Scientific - peer-reviewArticle

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

VL - 46

SP - 170

EP - 182

JO - Behavior Genetics

T2 - Behavior Genetics

JF - Behavior Genetics

SN - 0001-8244

IS - 2

ER -

van den Berg SM, de Moor MHM, Verweij CJH, Krueger RF, Luciano M, Vasquez AA et al. Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium. Behavior Genetics. 2016;46(2):170-182. Available from, DOI: 10.1007/s10519-015-9735-5