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Behav Genet. 2016 Mar;46(2):170-82. doi: 10.1007/s10519-015-9735-5. Epub 2015 Sep 11.

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

van den Berg SM1, de Moor MH2,3,4, Verweij KJ5,6, Krueger RF7, Luciano M8,9, Arias Vasquez A10,11,12,13, Matteson LK7, Derringer J14, Esko T15, Amin N16, Gordon SD5, Hansell NK5, Hart AB17, Seppälä I18, Huffman JE19, Konte B20, Lahti J21,22, Lee M23, Miller M7, Nutile T24, Tanaka T25, Teumer A26, Viktorin A27, Wedenoja J28, Abdellaoui A2, Abecasis GR29, Adkins DE30, Agrawal A31, Allik J32,33, Appel K34, Bigdeli TB23, Busonero F35, Campbell H36, Costa PT37, Smith GD38, Davies G8,9, de Wit H39, Ding J40, Engelhardt BE41, Eriksson JG22,42,43,44,45, Fedko IO2, Ferrucci L25, Franke B10,11,12, Giegling I20, Grucza R31, Hartmann AM20, Heath AC31, Heinonen K21, Henders AK5, Homuth G46, Hottenga JJ2, Iacono WG7, Janzing J11, Jokela M21, Karlsson R27, Kemp JP38,47, Kirkpatrick MG39, Latvala A28,42, Lehtimäki T18, Liewald DC8,9, Madden PA31, Magri C48, Magnusson PK27, Marten J19, Maschio A35, Mbarek H2, Medland SE5, Mihailov E15,49, Milaneschi Y50, Montgomery GW5, Nauck M51, Nivard MG2, Ouwens KG2, Palotie A52,53, Pettersson E27, Polasek O54, Qian Y40, Pulkki-Råback L21, Raitakari OT55,56, Realo A32, Rose RJ57, Ruggiero D24, Schmidt CO26, Slutske WS58, Sorice R24, Starr JM9,59, St Pourcain B38,60,61, Sutin AR25,62, Timpson NJ38, Trochet H19, Vermeulen S12,63, Vuoksimaa E28, Widen E53, Wouda J64,2, Wright MJ5, Zgaga L36,65; Generation Scotland, Porteous D66, Minelli A48, Palmer AA17,39, Rujescu D20, Ciullo M24, Hayward C19, Rudan I36, Metspalu A15,33, Kaprio J28,42,53, Deary IJ8,9, Räikkönen K21, Wilson JF19,36, Keltikangas-Järvinen L21, Bierut LJ31, Hettema JM23, Grabe HJ34,67, Penninx BW50, van Duijn CM16, Evans DM38, Schlessinger D40, Pedersen NL27, Terracciano A22,25, McGue M7,68, Martin NG5, Boomsma DI2.

Author information

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.

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

PMID:
26362575
PMCID:
PMC4751159
DOI:
10.1007/s10519-015-9735-5
[Indexed for MEDLINE]
Free PMC Article

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