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.
authors.affiliation: 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.
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authors.affiliation: Donders Institute for Cognitive Neuroscience, Radboud University Nijmegen, Nijmegen, The Netherlands.|Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.|Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.|Department of Cognitive Neuroscience, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
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authors.affiliation: Estonian Genome Center, University of Tartu, Tartu, Estonia.|Department of Biotechnology, University of Tartu, Tartu, Estonia.
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authors.affiliation: Department of Psychiatry, EMGO+ Institute, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
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authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.|Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
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authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.|Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
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authors.affiliation: MRC Human Genetics Unit, MRC IGMM, Western General Hospital, University of Edinburgh, Edinburgh, UK.
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authors.affiliation: Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.|Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Sita
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authors.affiliation: 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.|Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
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authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
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authors.affiliation: Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.|Department of Public Health and Primary Care, Trinity College Dublin, Dublin, Ireland.
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authors.affiliation: Medical Genetics Section, Centre for Genomics and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, The University of Edinburgh, Edinburgh, UK.
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authors.lastname: Metspalu
authors.affiliation: Department of Public Health, University of Helsinki, Helsinki, Finland.|National Institute for Health and Welfare (THL), Helsinki, Finland.|Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
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authors.affiliation: Department of Psychology, University of Edinburgh, Edinburgh, UK.|Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
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authors.affiliation: Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
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authors.affiliation: MRC Human Genetics Unit, MRC IGMM, Western General Hospital, University of Edinburgh, Edinburgh, UK.|Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
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authors.affiliation: Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
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authors.affiliation: Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.|Department of Psychiatry and Psychotherapy, HELIOS Hospital Stralsund, Stralsund, Germany.
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authors.affiliation: Department of Psychiatry, EMGO+ Institute, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
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authors.affiliation: Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.affiliation: Medical Research Council Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.affiliation: Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
authors.forename: David
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authors.lastname: Schlessinger
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Pedersen
authors.affiliation: Folkhälsan Research Center, Helsinki, Finland.|National Institute on Aging, NIH, Baltimore, MD, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Terracciano
authors.affiliation: Department of Psychology, University of Minnesota, Minneapolis, USA.|Institute of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Matt
authors.initials: M
authors.lastname: McGue
authors.affiliation: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors.forename: Nicholas G
authors.initials: NG
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authors.affiliation: Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Dorret I
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mesh_terms: D015331:Cohort Studies; D005120:Extraversion, Psychological; D055106:Genome-Wide Association Study; D006801:Humans; D020412:Multifactorial Inheritance / Q000235:genetics; D010551:Personality / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors
keywords: Common genetic variants; Imputation; Personality; Phenotype harmonization; Polygenic risk