Abstract

Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genome-wide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit–hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety).

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Acknowledgements

We thank the customers, research participants and employees of 23andMe for making this work possible. This project was funded by National Institute of Mental Health R01MH100351 (M.-T.L., N.S. and C.-H.C.), NARSAD Young Investigator award (C.-H.C.), South-East Norway Regional Health Authority (2016-064) (O.B.S.), and Research Council of Norway through a FRIPRO Mobility Grant, contract no. 251134 (Y.W.). The FRIPRO Mobility grant scheme (FRICON) is cofunded by the European Union's Seventh Framework Programme for research, technological development and demonstration under Marie Curie grant agreement no. 608695. D.J.S. is supported by a Lister Institute Prize fellowship. The research leading to deCODE results was supported in part by the US National Institutes of Health NIDA (R01-DA017932 and R01-DA034076) and the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115008, of which resources are composed of a European Federation of Pharmaceutical Industries and Associations (EFPIA) in-kind contribution and financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EU-funded FP7-People-2011-IAPP grant PsychDPC (GA 28613) (H.S., G.B., T.E.T. and K.S.).

Author information

Affiliations

  1. Department of Radiology, University of California, San Diego, La Jolla, California, USA.

    • Min-Tzu Lo
    • , Chun-Chieh Fan
    • , Andrew Schork
    • , Karolina Kauppi
    • , Nilotpal Sanyal
    • , Linda K McEvoy
    • , Anders M Dale
    •  & Chi-Hua Chen
  2. 23andMe, Inc., Mountain View, California, USA.

    • David A Hinds
    •  & Joyce Y Tung
  3. Department of Psychiatry, University of California, San Diego, La Jolla, California, USA.

    • Carol Franz
    •  & Anders M Dale
  4. Department of Cognitive Science, University of California, San Diego, La Jolla, California, USA.

    • Chun-Chieh Fan
    •  & Andrew Schork
  5. Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.

    • Yunpeng Wang
    • , Dominic Holland
    •  & Anders M Dale
  6. NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

    • Yunpeng Wang
    • , Olav B Smeland
    •  & Ole A Andreassen
  7. Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

    • Yunpeng Wang
    • , Olav B Smeland
    •  & Ole A Andreassen
  8. Department of Radiation Sciences, Umea University, Sweden.

    • Karolina Kauppi
  9. MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.

    • Valentina Escott-Price
    •  & Michael O'Donovan
  10. Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.

    • Daniel J Smith
  11. deCODE Genetics/Amgen, Reykjavik, Iceland.

    • Hreinn Stefansson
    • , Gyda Bjornsdottir
    • , Thorgeir E Thorgeirsson
    •  & Kari Stefansson

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Contributions

C.-H.C., M.-T.L. and O.A.A. designed the study. M.-T.L. and C.-H.C. analyzed data and wrote the manuscript. D.A.H. and J.Y.T. analyzed the 23andMe data. V.E.-P., D.J.S. and M.O. analyzed the UK Biobank data. H.S., G.B., T.E.T. and K.S. analyzed the deCODE data. C.F., C.-C.F., Y.W., O.B.S., A.S., D.H., K.K., N.S., L.K.M., A.M.D. and O.A.A. contributed to manuscript preparation. All authors commented on and approved the manuscript.

Competing interests

H.S., T.E.T., G.B. and K.S. are employees of deCODE Genetics/Amgen. D.A.H. and J.Y.T. are employees of 23andMe, Inc.

Corresponding author

Correspondence to Chi-Hua Chen.

Integrated supplementary information

Supplementary information

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  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–6, Supplementary Tables 1–5, and Supplementary Note

Text files

  1. 1.

    Supplementary Data Set 1

    Agreeableness

  2. 2.

    Supplementary Data Set 2

    Conscientiousness

  3. 3.

    Supplementary Data Set 3

    Extraversion

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    Supplementary Data Set 4

    Neuroticism

  5. 5.

    Supplementary Data Set 5

    Openness

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DOI

https://doi.org/10.1038/ng.3736

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