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

Stéphanie M. van den Berg; Marleen H.M. de Moor; Karin J.H. Verweij; Robert F. Krueger; Michelle Luciano; Alejandro Arias Vasquez; Lindsay K. Matteson; Jaime Derringer; Tõnu Esko; Najaf Amin; Scott D. Gordon; Narelle K. Hansell; Amy B. Hart; Ilkka Seppälä; Jennifer E. Huffman; Bettina Konte; Jari Lahti; Minyoung Lee; Mike Miller; Teresa Nutile; Toshiko Tanaka; Alexander Teumer; Alexander Viktorin; Juho Wedenoja; Abdel Abdellaoui; Goncalo R. Abecasis; Daniel E. Adkins; Arpana Agrawal; Jüri Allik; Katja Appel; Timothy B. Bigdeli; Fabio Busonero; Harry Campbell; Paul T. Costa; George Davey Smith; Gail Davies; Harriet de Wit; Jun Ding; Barbara Engelhardt Martin; Johan G. Eriksson; Iryna O. Fedko; Luigi Ferrucci; Barbara Franke; Ina Giegling; Richard Grucza; Annette M. Hartmann; Andrew C. Heath; Kati Heinonen; Anjali K. Henders; Georg Homuth; Jouke Jan Hottenga; William G. Iacono; Joost Janzing; Markus Jokela; Robert Karlsson; John P. Kemp; Matthew G. Kirkpatrick; Antti Latvala; Terho Lehtimäki; David C. Liewald; Pamela A.F. Madden; Chiara Magri; Patrik K.E. Magnusson; Jonathan Marten; Andrea Maschio; Hamdi Mbarek; Sarah E. Medland; Evelin Mihailov; Yuri Milaneschi; Grant W. Montgomery; Matthias Nauck; Michel G. Nivard; Klaasjan G. Ouwens; Aarno Palotie; Erik Pettersson; Ozren Polasek; Yong Qian; Laura Pulkki-Råback; Olli T. Raitakari; Anu Realo; Richard J. Rose; Daniela Ruggiero; Carsten O. Schmidt; Wendy S. Slutske; Rossella Sorice; John M. Starr; Beate St Pourcain; Angelina R. Sutin; Nicholas J. Timpson; Holly Trochet; Sita Vermeulen; Eero Vuoksimaa; Elisabeth Widen; Jasper Wouda; Margaret J. Wright; Lina Zgaga; Scotland Generation Scotland; David Porteous; Alessandra Minelli; Abraham A. Palmer; Dan Rujescu; Marina Ciullo; Caroline Hayward; Igor Rudan; Andres Metspalu; Jaakko Kaprio; Ian J. Deary; Katri Räikkönen; James F. Wilson; Liisa Keltikangas-Järvinen; Laura J. Bierut; John M. Hettema; Hans J. Grabe; Brenda W.J.H. Penninx; Cornelia M. van Duijn; David M. Evans; David Schlessinger; Nancy L. Pedersen; Antonio Terracciano; Matt McGue; Nicholas G. Martin; Dorret 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

Stéphanie M. van den Berg, Marleen H.M. de Moor, Karin J.H. Verweij, Robert F. Krueger, Michelle Luciano, Alejandro Arias Vasquez, Lindsay K. Matteson, Jaime Derringer, Tõnu Esko, Najaf Amin, Scott D. Gordon, Narelle K. Hansell, Amy B. Hart, Ilkka Seppälä, Jennifer E. Huffman, Bettina Konte, Jari Lahti, Minyoung Lee, Mike Miller, Teresa NutileToshiko Tanaka, Alexander Teumer, Alexander Viktorin, Juho Wedenoja, Abdel Abdellaoui, Goncalo R. Abecasis, Daniel E. Adkins, Arpana Agrawal, Jüri Allik, Katja Appel, Timothy B. Bigdeli, Fabio Busonero, Harry Campbell, Paul T. Costa, George Davey Smith, Gail Davies, Harriet de Wit, Jun Ding, Barbara Engelhardt Martin, Johan G. Eriksson, Iryna O. Fedko, Luigi Ferrucci, Barbara Franke, Ina Giegling, Richard Grucza, Annette M. Hartmann, Andrew C. Heath, Kati Heinonen, Anjali K. Henders, Georg Homuth, Jouke Jan Hottenga, William G. Iacono, Joost Janzing, Markus Jokela, Robert Karlsson, John P. Kemp, Matthew G. Kirkpatrick, Antti Latvala, Terho Lehtimäki, David C. Liewald, Pamela A.F. Madden, Chiara Magri, Patrik K.E. Magnusson, Jonathan Marten, Andrea Maschio, Hamdi Mbarek, Sarah E. Medland, Evelin Mihailov, Yuri Milaneschi, Grant W. Montgomery, Matthias Nauck, Michel G. Nivard, Klaasjan G. Ouwens, Aarno Palotie, Erik Pettersson, Ozren Polasek, Yong Qian, Laura Pulkki-Råback, Olli T. Raitakari, Anu Realo, Richard J. Rose, Daniela Ruggiero, Carsten O. Schmidt, Wendy S. Slutske, Rossella Sorice, John M. Starr, Beate St Pourcain, Angelina R. Sutin, Nicholas J. Timpson, Holly Trochet, Sita Vermeulen, Eero Vuoksimaa, Elisabeth Widen, Jasper Wouda, Margaret J. Wright, Lina Zgaga, Scotland Generation Scotland, David Porteous, Alessandra Minelli, Abraham A. Palmer, Dan Rujescu, Marina Ciullo, Caroline Hayward, Igor Rudan, Andres Metspalu, Jaakko Kaprio, Ian J. Deary, Katri Räikkönen, James F. Wilson, Liisa Keltikangas-Järvinen, Laura J. Bierut, John M. Hettema, Hans J. Grabe, Brenda W.J.H. Penninx, Cornelia M. van Duijn, David M. Evans, David Schlessinger, Nancy L. Pedersen, Antonio Terracciano, Matt McGue, Nicholas G. Martin, Dorret I. Boomsma

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110 Scopus citations

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 (US)
Pages (from-to)	170-182
Number of pages	13
Journal	Behavior Genetics
Volume	46
Issue number	2
DOIs	https://doi.org/10.1007/s10519-015-9735-5
State	Published - Mar 1 2016

All Science Journal Classification (ASJC) codes

Ecology, Evolution, Behavior and Systematics
Genetics
Genetics(clinical)

Keywords

Common genetic variants
Imputation
Personality
Phenotype harmonization
Polygenic risk

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10.1007/s10519-015-9735-5

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van den Berg, S. M., de Moor, M. H. M., Verweij, K. J. H., Krueger, R. F., Luciano, M., Arias Vasquez, 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., Lee, M., Miller, M., ... 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

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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.",

keywords = "Common genetic variants, Imputation, Personality, Phenotype harmonization, Polygenic risk",

author = "{van den Berg}, {St{\'e}phanie M.} and {de Moor}, {Marleen H.M.} and Verweij, {Karin J.H.} and Krueger, {Robert F.} and Michelle Luciano and {Arias Vasquez}, Alejandro and Matteson, {Lindsay K.} and Jaime Derringer and T{\~o}nu Esko and Najaf Amin and Gordon, {Scott D.} and Hansell, {Narelle K.} and Hart, {Amy B.} and Ilkka Sepp{\"a}l{\"a} and Huffman, {Jennifer E.} and Bettina Konte and Jari Lahti and Minyoung Lee and Mike Miller and Teresa Nutile and Toshiko Tanaka and Alexander Teumer and Alexander Viktorin and Juho Wedenoja and Abdel Abdellaoui and Abecasis, {Goncalo R.} and Adkins, {Daniel E.} and Arpana Agrawal and J{\"u}ri Allik and Katja Appel and Bigdeli, {Timothy B.} and Fabio Busonero and Harry Campbell and Costa, {Paul T.} and Smith, {George Davey} and Gail Davies and {de Wit}, Harriet and Jun Ding and {Engelhardt Martin}, Barbara and Eriksson, {Johan G.} and Fedko, {Iryna O.} and Luigi Ferrucci and Barbara Franke and Ina Giegling and Richard Grucza and Hartmann, {Annette M.} and Heath, {Andrew C.} and Kati Heinonen and Henders, {Anjali K.} and Georg Homuth and Hottenga, {Jouke Jan} and Iacono, {William G.} and Joost Janzing and Markus Jokela and Robert Karlsson and Kemp, {John P.} and Kirkpatrick, {Matthew G.} and Antti Latvala and Terho Lehtim{\"a}ki and Liewald, {David C.} and Madden, {Pamela A.F.} and Chiara Magri and Magnusson, {Patrik K.E.} and Jonathan Marten and Andrea Maschio and Hamdi Mbarek and Medland, {Sarah E.} and Evelin Mihailov and Yuri Milaneschi and Montgomery, {Grant W.} and Matthias Nauck and Nivard, {Michel G.} and Ouwens, {Klaasjan G.} and Aarno Palotie and Erik Pettersson and Ozren Polasek and Yong Qian and Laura Pulkki-R{\aa}back and Raitakari, {Olli T.} and Anu Realo and Rose, {Richard J.} and Daniela Ruggiero and Schmidt, {Carsten O.} and Slutske, {Wendy S.} and Rossella Sorice and Starr, {John M.} and {St Pourcain}, Beate and Sutin, {Angelina R.} and Timpson, {Nicholas J.} and Holly Trochet and Sita Vermeulen and Eero Vuoksimaa and Elisabeth Widen and Jasper Wouda and Wright, {Margaret J.} and Lina Zgaga and {Generation Scotland}, Scotland and David Porteous and Alessandra Minelli and Palmer, {Abraham A.} and Dan Rujescu and Marina Ciullo and Caroline Hayward and Igor Rudan and Andres Metspalu and Jaakko Kaprio and Deary, {Ian J.} and Katri R{\"a}ikk{\"o}nen and Wilson, {James F.} and Liisa Keltikangas-J{\"a}rvinen and Bierut, {Laura J.} and Hettema, {John M.} and Grabe, {Hans J.} and Penninx, {Brenda W.J.H.} and {van Duijn}, {Cornelia M.} and Evans, {David M.} and David Schlessinger and Pedersen, {Nancy L.} and Antonio Terracciano and Matt McGue and Martin, {Nicholas G.} and Boomsma, {Dorret I.}",

note = "Publisher Copyright: {\textcopyright} 2015, The Author(s).",

year = "2016",

month = mar,

day = "1",

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

language = "English (US)",

volume = "46",

pages = "170--182",

journal = "Behavior Genetics",

issn = "0001-8244",

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van den Berg, SM, de Moor, MHM, Verweij, KJH, Krueger, RF, Luciano, M, Arias Vasquez, A, Matteson, LK, Derringer, J, Esko, T, Amin, N, Gordon, SD, Hansell, NK, Hart, AB, Seppälä, I, Huffman, JE, Konte, B, Lahti, J, Lee, M, 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, Smith, GD, Davies, G, de Wit, H, Ding, J, Engelhardt Martin, B, 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-Råback, 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, Vermeulen, S, Vuoksimaa, E, Widen, E, Wouda, J, Wright, MJ, Zgaga, L, Generation Scotland, S, 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

T2 - Findings from the Genetics of Personality Consortium

AU - van den Berg, Stéphanie M.

AU - de Moor, Marleen H.M.

AU - Verweij, Karin J.H.

AU - Krueger, Robert F.

AU - Luciano, Michelle

AU - Arias Vasquez, Alejandro

AU - Matteson, Lindsay K.

AU - Derringer, Jaime

AU - Esko, Tõnu

AU - Amin, Najaf

AU - Gordon, Scott D.

AU - Hansell, Narelle K.

AU - Hart, Amy B.

AU - Seppälä, Ilkka

AU - Huffman, Jennifer E.

AU - Konte, Bettina

AU - Lahti, Jari

AU - Lee, Minyoung

AU - Miller, Mike

AU - Nutile, Teresa

AU - Tanaka, Toshiko

AU - Teumer, Alexander

AU - Viktorin, Alexander

AU - Wedenoja, Juho

AU - Abdellaoui, Abdel

AU - Abecasis, Goncalo R.

AU - Adkins, Daniel E.

AU - Agrawal, Arpana

AU - Allik, Jüri

AU - Appel, Katja

AU - Bigdeli, Timothy B.

AU - Busonero, Fabio

AU - Campbell, Harry

AU - Costa, Paul T.

AU - Smith, George Davey

AU - Davies, Gail

AU - de Wit, Harriet

AU - Ding, Jun

AU - Engelhardt Martin, Barbara

AU - Eriksson, Johan G.

AU - Fedko, Iryna O.

AU - Ferrucci, Luigi

AU - Franke, Barbara

AU - Giegling, Ina

AU - Grucza, Richard

AU - Hartmann, Annette M.

AU - Heath, Andrew C.

AU - Heinonen, Kati

AU - Henders, Anjali K.

AU - Homuth, Georg

AU - Hottenga, Jouke Jan

AU - Iacono, William G.

AU - Janzing, Joost

AU - Jokela, Markus

AU - Karlsson, Robert

AU - Kemp, John P.

AU - Kirkpatrick, Matthew G.

AU - Latvala, Antti

AU - Lehtimäki, Terho

AU - Liewald, David C.

AU - Madden, Pamela A.F.

AU - Magri, Chiara

AU - Magnusson, Patrik K.E.

AU - Marten, Jonathan

AU - Maschio, Andrea

AU - Mbarek, Hamdi

AU - Medland, Sarah E.

AU - Mihailov, Evelin

AU - Milaneschi, Yuri

AU - Montgomery, Grant W.

AU - Nauck, Matthias

AU - Nivard, Michel G.

AU - Ouwens, Klaasjan G.

AU - Palotie, Aarno

AU - Pettersson, Erik

AU - Polasek, Ozren

AU - Qian, Yong

AU - Pulkki-Råback, Laura

AU - Raitakari, Olli T.

AU - Realo, Anu

AU - Rose, Richard J.

AU - Ruggiero, Daniela

AU - Schmidt, Carsten O.

AU - Slutske, Wendy S.

AU - Sorice, Rossella

AU - Starr, John M.

AU - St Pourcain, Beate

AU - Sutin, Angelina R.

AU - Timpson, Nicholas J.

AU - Trochet, Holly

AU - Vermeulen, Sita

AU - Vuoksimaa, Eero

AU - Widen, Elisabeth

AU - Wouda, Jasper

AU - Wright, Margaret J.

AU - Zgaga, Lina

AU - Generation Scotland, Scotland

AU - Porteous, David

AU - Minelli, Alessandra

AU - Palmer, Abraham A.

AU - Rujescu, Dan

AU - Ciullo, Marina

AU - Hayward, Caroline

AU - Rudan, Igor

AU - Metspalu, Andres

AU - Kaprio, Jaakko

AU - Deary, Ian J.

AU - Räikkönen, Katri

AU - Wilson, James F.

AU - Keltikangas-Järvinen, Liisa

AU - Bierut, Laura J.

AU - Hettema, John M.

AU - Grabe, Hans J.

AU - Penninx, Brenda W.J.H.

AU - van Duijn, Cornelia M.

AU - Evans, David M.

AU - Schlessinger, David

AU - Pedersen, Nancy L.

AU - Terracciano, Antonio

AU - McGue, Matt

AU - Martin, Nicholas G.

AU - Boomsma, Dorret I.

PY - 2016/3/1

Y1 - 2016/3/1

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.

KW - Common genetic variants

KW - Imputation

KW - Personality

KW - Phenotype harmonization

KW - Polygenic risk

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UR - http://www.scopus.com/inward/citedby.url?scp=84957952518&partnerID=8YFLogxK

U2 - 10.1007/s10519-015-9735-5

DO - 10.1007/s10519-015-9735-5

M3 - Article

C2 - 26362575

AN - SCOPUS:84957952518

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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