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

Stéphanie M van den Berg¹, Marleen H M de Moor^{2

3

4}, Karin J H Verweij^{5

6}, Robert F Krueger⁷, Michelle Luciano^{8

9}, Alejandro Arias Vasquez^{10

11

12

13}, Lindsay K Matteson⁷, Jaime Derringer¹⁴, Tõnu Esko¹⁵, Najaf Amin¹⁶, Scott D Gordon⁵, Narelle K Hansell⁵, Amy B Hart¹⁷, Ilkka Seppälä¹⁸, Jennifer E Huffman¹⁹, Bettina Konte²⁰, Jari Lahti^{21

22}, Minyoung Lee²³, Mike Miller⁷, Teresa Nutile²⁴, Toshiko Tanaka²⁵, Alexander Teumer²⁶, Alexander Viktorin²⁷, Juho Wedenoja²⁸, Abdel Abdellaoui², Goncalo R Abecasis²⁹, Daniel E Adkins³⁰, Arpana Agrawal³¹, Jüri Allik^{32

33}, Katja Appel³⁴, Timothy B Bigdeli²³, Fabio Busonero³⁵, Harry Campbell³⁶, Paul T Costa³⁷, George Davey Smith³⁸, Gail Davies^{8

9}, Harriet de Wit³⁹, Jun Ding⁴⁰, Barbara E Engelhardt⁴¹, Johan G Eriksson^{22

42

43

44

45}, Iryna O Fedko², Luigi Ferrucci²⁵, Barbara Franke^{10

11

12}, Ina Giegling²⁰, Richard Grucza³¹, Annette M Hartmann²⁰, Andrew C Heath³¹, Kati Heinonen²¹, Anjali K Henders⁵, Georg Homuth⁴⁶, Jouke-Jan Hottenga², William G Iacono⁷, Joost Janzing¹¹, Markus Jokela²¹, Robert Karlsson²⁷, John P Kemp^{38

47}, Matthew G Kirkpatrick³⁹, Antti Latvala^{28

42}, Terho Lehtimäki¹⁸, David C Liewald^{8

9}, Pamela A F Madden³¹, Chiara Magri⁴⁸, Patrik K E Magnusson²⁷, Jonathan Marten¹⁹, Andrea Maschio³⁵, Hamdi Mbarek², Sarah E Medland⁵, Evelin Mihailov^{15

49}, Yuri Milaneschi⁵⁰, Grant W Montgomery⁵, Matthias Nauck⁵¹, Michel G Nivard², Klaasjan G Ouwens², Aarno Palotie^{52

53}, Erik Pettersson²⁷, Ozren Polasek⁵⁴, Yong Qian⁴⁰, Laura Pulkki-Råback²¹, Olli T Raitakari^{55

56}, Anu Realo³², Richard J Rose⁵⁷, Daniela Ruggiero²⁴, Carsten O Schmidt²⁶, Wendy S Slutske⁵⁸, Rossella Sorice²⁴, John M Starr^{9

59}, Beate St Pourcain^{38

60

61}, Angelina R Sutin^{25

62}, Nicholas J Timpson³⁸, Holly Trochet¹⁹, Sita Vermeulen^{12

63}, Eero Vuoksimaa²⁸, Elisabeth Widen⁵³, Jasper Wouda^{64

2}, Margaret J Wright⁵, Lina Zgaga^{36

65}; Generation Scotland; David Porteous⁶⁶, Alessandra Minelli⁴⁸, Abraham A Palmer^{17

39}, Dan Rujescu²⁰, Marina Ciullo²⁴, Caroline Hayward¹⁹, Igor Rudan³⁶, Andres Metspalu^{15

33}, Jaakko Kaprio^{28

42

53}, Ian J Deary^{8

9}, Katri Räikkönen²¹, James F Wilson^{19

36}, Liisa Keltikangas-Järvinen²¹, Laura J Bierut³¹, John M Hettema²³, Hans J Grabe^{34

67}, Brenda W J H Penninx⁵⁰, Cornelia M van Duijn¹⁶, David M Evans³⁸, David Schlessinger⁴⁰, Nancy L Pedersen²⁷, Antonio Terracciano^{22

25}, Matt McGue^{7

68}, Nicholas G Martin⁵, Dorret I Boomsma²

Affiliations

¹ Department of Research Methodology, Measurement and Data-Analysis (OMD), Faculty of Behavioural, Management, and Social Sciences, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands. stephanie.vandenberg@utwente.nl.
² Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
³ Department of Clinical Child and Family Studies, VU University Amsterdam, Amsterdam, The Netherlands.
⁴ Department of Methods, VU University Amsterdam, Amsterdam, The Netherlands.
⁵ QIMR Berghofer Medical Research Institute, Brisbane, Australia.
⁶ Department of Developmental Psychology and EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, The Netherlands.
⁷ Department of Psychology, University of Minnesota, Minneapolis, USA.
⁸ Department of Psychology, University of Edinburgh, Edinburgh, UK.
⁹ Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
¹⁰ Donders Institute for Cognitive Neuroscience, Radboud University Nijmegen, Nijmegen, The Netherlands.
¹¹ Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
¹² Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
¹³ Department of Cognitive Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
¹⁴ Department of Psychology, University of Illinois at Urbana-Champaign, Champaign, IL, USA.
¹⁵ Estonian Genome Center, University of Tartu, Tartu, Estonia.
¹⁶ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
¹⁷ Department of Human Genetics, University of Chicago, Chicago, IL, USA.
¹⁸ Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
¹⁹ MRC Human Genetics Unit, MRC IGMM, Western General Hospital, University of Edinburgh, Edinburgh, UK.
²⁰ Department of Psychiatry, University of Halle, Halle, Germany.
²¹ Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
²² Folkhälsan Research Center, Helsinki, Finland.
²³ Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
²⁴ Institute of Genetics and Biophysics "A. Buzzati-Traverso" - CNR, Naples, Italy.
²⁵ National Institute on Aging, NIH, Baltimore, MD, USA.
²⁶ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
²⁷ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
²⁸ Department of Public Health, University of Helsinki, Helsinki, Finland.
²⁹ Department of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
³⁰ Pharmacotherapy & Outcomes Science, Virginia Commonwealth University, Richmond, VA, USA.
³¹ Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
³² Department of Psychology, University of Tartu, Tartu, Estonia.
³³ Estonian Academy of Sciences, Tallinn, Estonia.
³⁴ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
³⁵ Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato, Italy.
³⁶ Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
³⁷ Behavioral Medicine Research Center, Duke University School of Medicine, Durham, NC, USA.
³⁸ Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
³⁹ Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, USA.
⁴⁰ Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
⁴¹ Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
⁴² National Institute for Health and Welfare (THL), Helsinki, Finland.
⁴³ Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
⁴⁴ Unit of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
⁴⁵ Vasa Central Hospital, Vaasa, Finland.
⁴⁶ Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
⁴⁷ Translational Research Institute, University of Queensland Diamantina Institute, Brisbane, Australia.
⁴⁸ Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
⁴⁹ Department of Biotechnology, University of Tartu, Tartu, Estonia.
⁵⁰ Department of Psychiatry, EMGO+ Institute, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
⁵¹ Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
⁵² Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
⁵³ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
⁵⁴ Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia.
⁵⁵ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
⁵⁶ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
⁵⁷ Department of Psychological & Brain Sciences, Indiana University, Bloomington, IN, USA.
⁵⁸ Department of Psychological Sciences and Missouri Alcoholism Research Center, University of Missouri, Columbia, MO, USA.
⁵⁹ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
⁶⁰ School of Oral and Dental Sciences, University of Bristol, Bristol, UK.
⁶¹ School of Experimental Psychology, University of Bristol, Bristol, UK.
⁶² College of Medicine, Florida State University, Tallahassee, FL, USA.
⁶³ Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
⁶⁴ Department of Research Methodology, Measurement and Data-Analysis (OMD), Faculty of Behavioural, Management, and Social Sciences, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands.
⁶⁵ Department of Public Health and Primary Care, Trinity College Dublin, Dublin, Ireland.
⁶⁶ Medical Genetics Section, Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, The University of Edinburgh, Edinburgh, UK.
⁶⁷ Department of Psychiatry and Psychotherapy, HELIOS Hospital Stralsund, Stralsund, Germany.
⁶⁸ Institute of Public Health, University of Southern Denmark, Odense, Denmark.

PMID: 26362575
PMCID: PMC4751159
DOI: 10.1007/s10519-015-9735-5

Meta-Analysis

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

Stéphanie M van den Berg et al. Behav Genet. 2016 Mar.

. 2016 Mar;46(2):170-82.

doi: 10.1007/s10519-015-9735-5. Epub 2015 Sep 11.

Authors

Affiliations

¹ Department of Research Methodology, Measurement and Data-Analysis (OMD), Faculty of Behavioural, Management, and Social Sciences, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands. stephanie.vandenberg@utwente.nl.
² Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
³ Department of Clinical Child and Family Studies, VU University Amsterdam, Amsterdam, The Netherlands.
⁴ Department of Methods, VU University Amsterdam, Amsterdam, The Netherlands.
⁵ QIMR Berghofer Medical Research Institute, Brisbane, Australia.
⁶ Department of Developmental Psychology and EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, The Netherlands.
⁷ Department of Psychology, University of Minnesota, Minneapolis, USA.
⁸ Department of Psychology, University of Edinburgh, Edinburgh, UK.
⁹ Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
¹⁰ Donders Institute for Cognitive Neuroscience, Radboud University Nijmegen, Nijmegen, The Netherlands.
¹¹ Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
¹² Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
¹³ Department of Cognitive Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
¹⁴ Department of Psychology, University of Illinois at Urbana-Champaign, Champaign, IL, USA.
¹⁵ Estonian Genome Center, University of Tartu, Tartu, Estonia.
¹⁶ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
¹⁷ Department of Human Genetics, University of Chicago, Chicago, IL, USA.
¹⁸ Department of Clinical Chemistry, Fimlab Laboratories and School of Medicine, University of Tampere, Tampere, Finland.
¹⁹ MRC Human Genetics Unit, MRC IGMM, Western General Hospital, University of Edinburgh, Edinburgh, UK.
²⁰ Department of Psychiatry, University of Halle, Halle, Germany.
²¹ Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
²² Folkhälsan Research Center, Helsinki, Finland.
²³ Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
²⁴ Institute of Genetics and Biophysics "A. Buzzati-Traverso" - CNR, Naples, Italy.
²⁵ National Institute on Aging, NIH, Baltimore, MD, USA.
²⁶ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
²⁷ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
²⁸ Department of Public Health, University of Helsinki, Helsinki, Finland.
²⁹ Department of Biostatistics, Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
³⁰ Pharmacotherapy & Outcomes Science, Virginia Commonwealth University, Richmond, VA, USA.
³¹ Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
³² Department of Psychology, University of Tartu, Tartu, Estonia.
³³ Estonian Academy of Sciences, Tallinn, Estonia.
³⁴ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
³⁵ Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Monserrato, Italy.
³⁶ Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
³⁷ Behavioral Medicine Research Center, Duke University School of Medicine, Durham, NC, USA.
³⁸ Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
³⁹ Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, USA.
⁴⁰ Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
⁴¹ Department of Biostatistics and Bioinformatics, Duke University, Durham, NC, USA.
⁴² National Institute for Health and Welfare (THL), Helsinki, Finland.
⁴³ Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
⁴⁴ Unit of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.
⁴⁵ Vasa Central Hospital, Vaasa, Finland.
⁴⁶ Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
⁴⁷ Translational Research Institute, University of Queensland Diamantina Institute, Brisbane, Australia.
⁴⁸ Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
⁴⁹ Department of Biotechnology, University of Tartu, Tartu, Estonia.
⁵⁰ Department of Psychiatry, EMGO+ Institute, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
⁵¹ Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
⁵² Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
⁵³ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
⁵⁴ Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia.
⁵⁵ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
⁵⁶ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
⁵⁷ Department of Psychological & Brain Sciences, Indiana University, Bloomington, IN, USA.
⁵⁸ Department of Psychological Sciences and Missouri Alcoholism Research Center, University of Missouri, Columbia, MO, USA.
⁵⁹ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
⁶⁰ School of Oral and Dental Sciences, University of Bristol, Bristol, UK.
⁶¹ School of Experimental Psychology, University of Bristol, Bristol, UK.
⁶² College of Medicine, Florida State University, Tallahassee, FL, USA.
⁶³ Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
⁶⁴ Department of Research Methodology, Measurement and Data-Analysis (OMD), Faculty of Behavioural, Management, and Social Sciences, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands.
⁶⁵ Department of Public Health and Primary Care, Trinity College Dublin, Dublin, Ireland.
⁶⁶ Medical Genetics Section, Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, The University of Edinburgh, Edinburgh, UK.
⁶⁷ Department of Psychiatry and Psychotherapy, HELIOS Hospital Stralsund, Stralsund, Germany.
⁶⁸ Institute of Public Health, University of Southern Denmark, Odense, Denmark.

PMID: 26362575
PMCID: PMC4751159
DOI: 10.1007/s10519-015-9735-5

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.

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Figures

**Fig. 1**
Manhattan plot for meta-analysis results of 29 discovery cohorts for extraversion in the Genetics of Personality Consortium

**Fig. 2**
Quantile-Quantile plots for meta-analysis results of 29 discovery cohorts for extraversion in the Genetics of Personality Consortium

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources