This is a preprint.

It has not yet been peer reviewed by a journal.

The National Library of Medicine is running a pilot to include preprints that result from research funded by NIH in PMC and PubMed.

[Preprint]. 2025 May 19:2025.05.16.648988.

doi: 10.1101/2025.05.16.648988.

Robust inference and widespread genetic correlates from a large-scale genetic association study of human personality

Ted Schwaba¹, Margaret L Clapp Sullivan², Wonuola A Akingbuwa^{3

4}, Kerli Ilves⁵, Peter T Tanksley⁶, Camille M Williams⁷, Yavor Dragostinov^{2

8}, Wangjingyi Liao⁹, Lindsay S Ackerman¹, Josephine C M Fealy¹, Gibran Hemani^{10

11}, Javier de la Fuente², Priya Gupta¹², Murray B Stein¹³, Joel Gelernter¹², Daniel F Levey¹², Urmo Võsa⁵, Liisi Ausmees¹⁴, Anu Realo^{14

15

16}; Estonian Biobank Research Team; Mariliis Vaht⁵, Jüri Allik¹⁴, Tõnu Esko⁵, René Mõttus^{14

17}, Uku Vainik^{5

14

18}, Gudrun A Jonsdottir¹⁹, Gudmar Thorleifsson¹⁹, Árni Freyr Gunnarsson¹⁹, Gyda Bjornsdottir¹⁹, Thorgeir E Thorgeirsson¹⁹, Hreinn Stefansson¹⁹, Kari Stefansson¹⁹, Rosa Cheesman^{20

21}, Qi Qin²⁰, Elizabeth C Corfield^{10

21

22}, Helga Ask^{20

21}, Fartein Ask Torvik^{20

23}, Eivind Ystrom^{20

21

24}, Martin Tesli^{25

26}, Dorret I Boomsma²⁷, Eco J C de Geus^{3

4}, Jouke-Jan Hottenga³, Dener Cardoso Melo²⁸, Harold Snieder²⁹, Catharina A Hartman^{17

28}, Charley Xia^{17

30}, Archie Campbell³¹, Michelle Luciano¹⁷, Ian J Deary^{17

30}, W David Hill^{17

30}, Seon-Kyeong Jang³², Scott I Vrieze^{33

34}, Gonçalo Abecasis³⁵, Michelle K Lupton^{36

37

38}, Brittany L Mitchell^{36

37

38}, Petra V Viher³⁶, Lucía Colodro-Conde³⁶, Nicholas G Martin³⁶, Sarah E Medland³⁶, Eske M Derks³⁶, Briar Wormington³⁶, Jaakko Kaprio³⁹, Karri Silventoinen⁴⁰, Teemu Palviainen³⁹, Agnieszka Gidziela⁹, Kaili Rimfeld^{41

42}, Robert Plomin⁴², Margherita Malanchini⁹, Danielle M Dick^{43

44}, Fazil Aliev⁴⁴; COGA Collaborators, The Spit for Science Working Group; Laura W Wesseldijk^{45

46

47}, Fredrik Ullén^{45

46}, Miriam A Mosing^{46

48

49}, Henry R Kranzler⁵⁰, Yaira Nunez⁵¹, Sarah Beck⁵¹, Renato Polimanti⁵¹, Tobias Edwards³³, Alexandros Giannelis³³, Emily A Willoughby³³, James J Lee³³, Matt McGue³³, Antonio Terracciano^{52

53}, Michele Marongiu⁵⁴, Edoardo Fiorillo⁵⁴, Francesco Cucca⁵⁵, Angelina R Sutin⁵⁶, Peter J van der Most²⁹, Albertine J Oldehinkel²⁸, Tina Kretschmer⁵⁷, Andrey A Shabalin⁵⁸, Anna R Docherty⁵⁸, Robert F Krueger³³, Colin D Freilich³³, Binisha H Mishra^{59

60

61}, Terho Lehtimäki^{59

60

61}, Olli T Raitakari^{62

63

64

65}, Mika Kähönen^{60

66}, Aino Saarinen⁶⁷, Henrik Dobewall⁶⁸, Liisa Keltikangas-Järvinen⁶⁷, Klaus Berger⁶⁹, Marisol Herrera-Rivero^{69

70}, Fabian Streit^{71

72

73}, Swapnil Awasthi⁷⁴, Stephanie H Witt⁷⁵, Johanna Tuhkanen⁷⁶, Katri Räikkönen⁷⁶, Johan G Eriksson^{77

78

79}, Jari Lahti^{76

78}, Gail Davies³⁰, Paul Redmond³⁰, Adele Taylor³⁰, Janie Corley³⁰, Tom C Russ^{80

81}, Marina Ciullo⁸², Teresa Nutile⁸², Jun Ding⁸³, Yong Qian⁸³, Toshiko Tanaka⁸³, Luigi Ferrucci⁸³, Lea Zillich⁷⁵, Lea Sirignano⁷⁵, K Paige Harden², Erhan Genç⁸⁴, Patrick D Gajewski⁸⁵, Stephan Getzmann⁸⁵, Christoph Fraenz⁸⁴, Javier E Schneider Peñate⁸⁶, Stefanie Lis^{87

88}, Alisha S M Hall^{75

89

90}, Christian Schmahl⁸⁷, Sabine C Herpertz⁹¹, Abdel Abdellaoui^{47

92}, Michel G Nivard^{10

11}, Elliot M Tucker-Drob^{2

8}

Affiliations

¹ Department of Psychology, Michigan State University, East Lansing, MI, USA.
² Department of Psychology, University of Texas at Austin, Austin, TX, USA.
³ Department of Biological Psychology, Faculty of Behavioural and Movement Sciences, Vrije Universiteit, Amsterdam, the Netherlands.
⁴ Amsterdam Public Health Research Institute, Amsterdam University Medical Centre, Amsterdam, the Netherlands.
⁵ Institute of Genomics, University of Tartu, Estonia.
⁶ ALERRT Center, Texas State University.
⁷ Laboratoire de Sciences Cognitives et Psycholinguistique (ENS, EHESS, CNRS), École Normale Supérieure, PSL University, Paris, France.
⁸ Population Research Center, University of Texas at Austin, Austin, TX, USA.
⁹ School of Biological and Behavioral Sciences, Queen Mary University of London, London, UK.
¹⁰ Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
¹¹ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
¹² Yale University, Veterans Affairs Connecticut Healthcare System.
¹³ University of California San Diego, Veterans Affairs San Diego Healthcare System.
¹⁴ Institute of Psychology, University of Tartu, Estonia.
¹⁵ Department of Psychology, University of Warwick, UK.
¹⁶ School of Educational Sciences, Tallinn University, Estonia.
¹⁷ Department of Psychology, University of Edinburgh, Edinburgh, UK.
¹⁸ Montreal Neurological Institute, McGill University, Canada.
¹⁹ deCODE genetics/Amgen, Reykjavik, Iceland.
²⁰ PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway.
²¹ PsychGen Centre for Genetic Epidemiology and Mental Health, Division of Public Health and Prevention, Norwegian Institute of Public Health, Oslo, Norway.
²² Psychiatric Genetic Epidemiology Group, Research Department, Lovisenberg Diaconal Hospital, Oslo, Norway.
²³ Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
²⁴ Centre for Research on Equality in Education, Faculty of Educational Sciences, University of Oslo, Oslo, Norway.
²⁵ Department of Mental Health, Norwegian Institute of Public Health, Oslo, Norway.
²⁶ Department of Psychiatry, Østfold Hospital, Norway.
²⁷ Department of Complex Trait Genetics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
²⁸ Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
²⁹ Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
³⁰ Lothian Birth Cohort Studies, Department of Psychology, University of Edinburgh, Edinburgh, UK.
³¹ Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
³² Department of Computational Medicine, University of California Los Angeles, Los Angeles.
³³ Department of Psychology, University of Minnesota.
³⁴ Minnesota Center for Twin and Family Research.
³⁵ Regeneron Genetics Center, Regeneron Pharmaceuticals.
³⁶ QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
³⁷ Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
³⁸ School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
³⁹ Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland.
⁴⁰ Population Research Unit, Faculty of Social Sciences, University of Helsinki, Helsinki, Finland.
⁴¹ Department of Psychology, Royal Holloway University of London, Egham, UK.
⁴² Social, Genetic, & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁴³ Rutgers Addiction Research Center, Brain Health Institute, Rutgers University.
⁴⁴ Department of Psychiatry, Rutgers Robert Wood Johnson Medical School.
⁴⁵ Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁴⁶ Department of Cognitive Neuropsychology, Max Planck Institute for Empirical Aesthetics, Frankfurt am Main, Germany.
⁴⁷ Department of Psychiatry, Amsterdam University Medical Centre, University of Amsterdam.
⁴⁸ Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁴⁹ Melbourne School of Psychological Sciences, University of Melbourne, Australia.
⁵⁰ Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.
⁵¹ Department of Psychiatry, Yale School of Medicine, New Haven CT, United States.
⁵² Department of Geriatrics, College of Medicine, Florida State University, Tallahassee.
⁵³ Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore.
⁵⁴ Institute for Genetic and Biomedical Research, Consiglio Nazionale delle Ricerche (CNR), Cagliari, Italy.
⁵⁵ Department of Biomedical Sciences, University Study of Sassari, Sassari, Italy.
⁵⁶ Department of Behavioral Sciences and Social Medicine, College of Medicine, Florida State University, Tallahassee.
⁵⁷ Pedagogical Sciences, Faculty of Behavioural and Social Sciences, University of Groningen, Groningen, The Netherlands.
⁵⁸ Huntsman Mental Health Institute, Department of Psychiatry, University of Utah.
⁵⁹ Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁶⁰ Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁶¹ Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
⁶² Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
⁶³ Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.
⁶⁴ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
⁶⁵ InFLAMES Research Flagship, University of Turku, Turku, Finland.
⁶⁶ Department of Clinical Physiology, Tampere University Hospital, Tampere Finland.
⁶⁷ Faculty of Medicine, Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
⁶⁸ Finnish Institute for Health and Welfare.
⁶⁹ Institute of Epidemiology and Social Medicine, University of Münster, Germany.
⁷⁰ Department of Genetic Epidemiology, Institute of Human Genetics, Germany.
⁷¹ Hector Institute for Artificial Intelligence in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁷² Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁷³ German Center for Mental Health (DZPG), Partner Site Mannheim - Heidelberg - Ulm, Germany.
⁷⁴ Department of Psychiatry and Psychotherapy, Campus Mitte Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁷⁵ Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim/Heidelberg University, Central Institute of Mental Health, Mannheim, Germany.
⁷⁶ Department of Psychology, University of Helsinki, Helsinki, Finland.
⁷⁷ Department of General Practice and Primary Health Care, Tukholmankatu 8 B, University of Helsinki, Finland.
⁷⁸ Folkhälsan Research Centre, Helsinki, Finland.
⁷⁹ National University Singapore, Yong Loo Lin School of Medicine, Department of Obstetrics and Gynecology, Singapore, Singapore.
⁸⁰ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, United Kingdom.
⁸¹ Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, United Kingdom.
⁸² Institute of Genetics and Biophysics "Adriano Buzzati-Traverso" - CNR, Naples, Italy.
⁸³ Translational Gerontology Branch, National Institute on Aging, Baltimore.
⁸⁴ Department of Psychology and Neurosciences, Neuroimaging and Interindividual Differences, Leibniz Research Centre for Working Environment and Human Factors (IfADo), Dortmund, Germany.
⁸⁵ Department of Ergonomics, Networking Group Aging, Leibniz Research Centre for Working Environment and Human Factors (IfADo), Dortmund, Germany.
⁸⁶ Department of Psychology, Neuropsychology, Ruhr University Bochum, Bochum, Germany.
⁸⁷ Department of Psychosomatic Medicine and Psychotherapy, Medical Faculty Mannheim/Heidelberg University, Central Institute of Mental Health, Mannheim, Germany.
⁸⁸ Department of Clinical Psychology, Medical Faculty Mannheim/Heidelberg University, Central Institute of Mental Health, Mannheim, Germany.
⁸⁹ Department of Affective Disorders, Aarhus University Hospital, Aarhus, Denmark.
⁹⁰ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
⁹¹ Department of Psychosomatic General Psychiatry, Center for Psychosocial Medicine, Medical Faculty Mannheim/Heidelberg University, Heidelberg, Germany.
⁹² Amsterdam Neuroscience, Amsterdam, The Netherlands.

PMID: 40475535
PMCID: PMC12139836
DOI: 10.1101/2025.05.16.648988

Robust inference and widespread genetic correlates from a large-scale genetic association study of human personality

Ted Schwaba et al. bioRxiv. 2025.

[Preprint]. 2025 May 19:2025.05.16.648988.

doi: 10.1101/2025.05.16.648988.

Authors

Affiliations

¹ Department of Psychology, Michigan State University, East Lansing, MI, USA.
² Department of Psychology, University of Texas at Austin, Austin, TX, USA.
³ Department of Biological Psychology, Faculty of Behavioural and Movement Sciences, Vrije Universiteit, Amsterdam, the Netherlands.
⁴ Amsterdam Public Health Research Institute, Amsterdam University Medical Centre, Amsterdam, the Netherlands.
⁵ Institute of Genomics, University of Tartu, Estonia.
⁶ ALERRT Center, Texas State University.
⁷ Laboratoire de Sciences Cognitives et Psycholinguistique (ENS, EHESS, CNRS), École Normale Supérieure, PSL University, Paris, France.
⁸ Population Research Center, University of Texas at Austin, Austin, TX, USA.
⁹ School of Biological and Behavioral Sciences, Queen Mary University of London, London, UK.
¹⁰ Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
¹¹ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
¹² Yale University, Veterans Affairs Connecticut Healthcare System.
¹³ University of California San Diego, Veterans Affairs San Diego Healthcare System.
¹⁴ Institute of Psychology, University of Tartu, Estonia.
¹⁵ Department of Psychology, University of Warwick, UK.
¹⁶ School of Educational Sciences, Tallinn University, Estonia.
¹⁷ Department of Psychology, University of Edinburgh, Edinburgh, UK.
¹⁸ Montreal Neurological Institute, McGill University, Canada.
¹⁹ deCODE genetics/Amgen, Reykjavik, Iceland.
²⁰ PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway.
²¹ PsychGen Centre for Genetic Epidemiology and Mental Health, Division of Public Health and Prevention, Norwegian Institute of Public Health, Oslo, Norway.
²² Psychiatric Genetic Epidemiology Group, Research Department, Lovisenberg Diaconal Hospital, Oslo, Norway.
²³ Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
²⁴ Centre for Research on Equality in Education, Faculty of Educational Sciences, University of Oslo, Oslo, Norway.
²⁵ Department of Mental Health, Norwegian Institute of Public Health, Oslo, Norway.
²⁶ Department of Psychiatry, Østfold Hospital, Norway.
²⁷ Department of Complex Trait Genetics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
²⁸ Interdisciplinary Center Psychopathology and Emotion Regulation (ICPE), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
²⁹ Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
³⁰ Lothian Birth Cohort Studies, Department of Psychology, University of Edinburgh, Edinburgh, UK.
³¹ Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
³² Department of Computational Medicine, University of California Los Angeles, Los Angeles.
³³ Department of Psychology, University of Minnesota.
³⁴ Minnesota Center for Twin and Family Research.
³⁵ Regeneron Genetics Center, Regeneron Pharmaceuticals.
³⁶ QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
³⁷ Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
³⁸ School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
³⁹ Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland.
⁴⁰ Population Research Unit, Faculty of Social Sciences, University of Helsinki, Helsinki, Finland.
⁴¹ Department of Psychology, Royal Holloway University of London, Egham, UK.
⁴² Social, Genetic, & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁴³ Rutgers Addiction Research Center, Brain Health Institute, Rutgers University.
⁴⁴ Department of Psychiatry, Rutgers Robert Wood Johnson Medical School.
⁴⁵ Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
⁴⁶ Department of Cognitive Neuropsychology, Max Planck Institute for Empirical Aesthetics, Frankfurt am Main, Germany.
⁴⁷ Department of Psychiatry, Amsterdam University Medical Centre, University of Amsterdam.
⁴⁸ Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
⁴⁹ Melbourne School of Psychological Sciences, University of Melbourne, Australia.
⁵⁰ Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.
⁵¹ Department of Psychiatry, Yale School of Medicine, New Haven CT, United States.
⁵² Department of Geriatrics, College of Medicine, Florida State University, Tallahassee.
⁵³ Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore.
⁵⁴ Institute for Genetic and Biomedical Research, Consiglio Nazionale delle Ricerche (CNR), Cagliari, Italy.
⁵⁵ Department of Biomedical Sciences, University Study of Sassari, Sassari, Italy.
⁵⁶ Department of Behavioral Sciences and Social Medicine, College of Medicine, Florida State University, Tallahassee.
⁵⁷ Pedagogical Sciences, Faculty of Behavioural and Social Sciences, University of Groningen, Groningen, The Netherlands.
⁵⁸ Huntsman Mental Health Institute, Department of Psychiatry, University of Utah.
⁵⁹ Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁶⁰ Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁶¹ Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
⁶² Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
⁶³ Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.
⁶⁴ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
⁶⁵ InFLAMES Research Flagship, University of Turku, Turku, Finland.
⁶⁶ Department of Clinical Physiology, Tampere University Hospital, Tampere Finland.
⁶⁷ Faculty of Medicine, Department of Psychology and Logopedics, University of Helsinki, Helsinki, Finland.
⁶⁸ Finnish Institute for Health and Welfare.
⁶⁹ Institute of Epidemiology and Social Medicine, University of Münster, Germany.
⁷⁰ Department of Genetic Epidemiology, Institute of Human Genetics, Germany.
⁷¹ Hector Institute for Artificial Intelligence in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁷² Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
⁷³ German Center for Mental Health (DZPG), Partner Site Mannheim - Heidelberg - Ulm, Germany.
⁷⁴ Department of Psychiatry and Psychotherapy, Campus Mitte Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany.
⁷⁵ Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim/Heidelberg University, Central Institute of Mental Health, Mannheim, Germany.
⁷⁶ Department of Psychology, University of Helsinki, Helsinki, Finland.
⁷⁷ Department of General Practice and Primary Health Care, Tukholmankatu 8 B, University of Helsinki, Finland.
⁷⁸ Folkhälsan Research Centre, Helsinki, Finland.
⁷⁹ National University Singapore, Yong Loo Lin School of Medicine, Department of Obstetrics and Gynecology, Singapore, Singapore.
⁸⁰ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, United Kingdom.
⁸¹ Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, United Kingdom.
⁸² Institute of Genetics and Biophysics "Adriano Buzzati-Traverso" - CNR, Naples, Italy.
⁸³ Translational Gerontology Branch, National Institute on Aging, Baltimore.
⁸⁴ Department of Psychology and Neurosciences, Neuroimaging and Interindividual Differences, Leibniz Research Centre for Working Environment and Human Factors (IfADo), Dortmund, Germany.
⁸⁵ Department of Ergonomics, Networking Group Aging, Leibniz Research Centre for Working Environment and Human Factors (IfADo), Dortmund, Germany.
⁸⁶ Department of Psychology, Neuropsychology, Ruhr University Bochum, Bochum, Germany.
⁸⁷ Department of Psychosomatic Medicine and Psychotherapy, Medical Faculty Mannheim/Heidelberg University, Central Institute of Mental Health, Mannheim, Germany.
⁸⁸ Department of Clinical Psychology, Medical Faculty Mannheim/Heidelberg University, Central Institute of Mental Health, Mannheim, Germany.
⁸⁹ Department of Affective Disorders, Aarhus University Hospital, Aarhus, Denmark.
⁹⁰ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
⁹¹ Department of Psychosomatic General Psychiatry, Center for Psychosocial Medicine, Medical Faculty Mannheim/Heidelberg University, Heidelberg, Germany.
⁹² Amsterdam Neuroscience, Amsterdam, The Netherlands.

PMID: 40475535
PMCID: PMC12139836
DOI: 10.1101/2025.05.16.648988

Abstract

Personality traits describe stable differences in how individuals think, feel, and behave and how they interact with and experience their social and physical environments. We assemble data from 46 cohorts including 611K-1.14M participants with European-like and African-like genomes for genome-wide association studies (GWAS) of the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism, and openness to experience), and data from 51K participants for within-family GWAS. We identify 1,257 lead genetic variants associated with personality, including 823 novel variants. Common genetic variants explain 4.8%-9.3% of the variance in each trait, and 10.5%-16.2% accounting for measurement unreliability. Genetic effects on personality are highly consistent across geography, reporter (self vs. close other), age group, and measurement instrument, and we find minimal spousal assortment for personality in recent history. In stark contrast to many other social and behavioral traits, within-family GWAS and polygenic index analyses indicate little to no shared environmental confounding in genetic associations with personality. Polygenic prediction, genetic correlation, and Mendelian randomization analyses indicate that personality genetics have widespread, potentially causal associations with a wide range of consequential behaviors and life outcomes. The genetic architecture of personality is robust and fundamental to being a human.

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Figures

**Figure 1.. Manhattan plots of Genome-Wide Associations for each Big Five personality trait (A-E) and genetic correlations across traits (F).**
Genome wide significance is denoted with a red line at p = 5×10⁻⁸. A selection of genes containing or nearby the most significant lead SNPs are annotated in each panel (Supplementary Tables S23–S27). Genetic correlations in panel F were estimated among EUR participants using LDSC; standard errors are in parentheses.

**Figure 2.. Polygenic prediction and additional genetic associations.**
Ext = Extraversion. Agr = Agreeableness. Con = Conscientiousness. Neu = Neuroticism. Ope = Openness to Experience. Panel A depicts standardized prediction of phenotypic personality trait scores among EUR and AFR participants in five cohorts using PGI weights derived from the EUR population-level GWAS. In panel B, betas for continuous traits are standardized and have point estimates depicted with circles, and betas for binary traits are logistic betas and have point estimates depicted with diamonds; percentage affirmative responses are noted in parentheses. † = questions asked only among a subgroup of participants (see Supplementary Text). Panel C depicts correlations between PGIs for each pair of family members. ‡ = Educational Attainment estimates come from Torvik et al. (2022), estimated across spouses in the MoBa cohort. In panel D, accelerometer activity indexes physical movement across a 24-hour period; see Grotzinger et al. (2022b) for complete details. Panel E depicts associations between PGI and census area of residence at age 50+, controlling for birthplace in addition to sex, age, array, and genetic principal components. Only associations that are significant at p < .01 after application of Benjamini-Hochberg false-discovery rate correction and sign-concordant within sibship are plotted. In all panels, error bars depict 95% confidence intervals. * = p < .01.

**Figure 3.. Genetic correlations between the Big Five personality traits and 67 behaviors and outcomes across 9 domains.**
E = Extraversion. A = Agreeableness. C = Conscientiousness. N = Neuroticism. O = Openness to experience. COVID = Coronavirus disease. HDL = High-density lipoprotein. LDL = Low-density lipoprotein. ADHD = Attention deficit hyperactivity disorder. Letters corresponding to personality traits represent correlation point estimates. Error bars represent 95% confidence intervals. Associations not significant at p < .01 are depicted in gray. Associations estimated using LDSC among EUR participants. Full description of each behavior and outcome are available in Supplementary Tables S31 and S32.

**Figure 4.. Evaluating environmental confounding in genetic associations with personality.**
In panel A, the magnitude of PGI prediction from the EUR population-level GWAS is presented for population-level and within-family analyses in two cohorts: Netherlands Twin Registry (NTR) and Twins Early Development Study (TEDS). In panel B, the magnitude of total PGI prediction from the EUR population-level GWAS among offspring in the deCODE cohort (with significance asterisks below the corresponding bar) is decomposed into directly transmitted and indirectly transmitted (non-inherited, with significance asterisks above the corresponding bar) genetic effects from parents (Supplementary Table S39). Comparison estimates for Educational Attainment (EA) come from a PGI constructed from the Okbay et al. (2022) GWAS of EA with deCODE and 23&Me cohorts held out. In panel C, h²_SNP estimates estimated with LDSC from the within-family GWAS (“Wit.”) are presented alongside full EUR population-level GWAS (“Full pop.,” Table 1) and matched population-level (“Pop.”) GWAS in cohorts that contributed to within-family GWAS (Supplementary Table S42). r_g below each pair of traits indicates their genetic correlation estimated with LDSC, with deviation from r_g = 1 tested using a nested chi-square model in Genomic SEM. p-values above each pair of traits indicates results of a test for differences in heritability between population and within-family estimates. In all panels, error bars depict 95% confidence intervals and standard errors are in parentheses. ns = p ≥ .05. * = p < .05. ** = p < .01. *** = p < .001.

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This is a preprint.

Robust inference and widespread genetic correlates from a large-scale genetic association study of human personality

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Robust inference and widespread genetic correlates from a large-scale genetic association study of human personality

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