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Causal influences of neuroticism on mental health and cardiovascular disease

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A Correction to this article was published on 09 July 2021

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Abstract

We investigated the relationship between neuroticism and 16 mental and 18 physical traits using summary results of genome-wide association studies for these traits. LD score regression was used to investigate genetic correlations between neuroticism and the 34 health outcomes. Mendelian randomization was performed to investigate mutual causal relationships between neuroticism and the 34 health outcomes. Neuroticism genetically correlates with a majority of health-related traits and confers causal effects on 12 mental traits (major depressive disorder (MDD), insomnia, subjective well-being (SWB, negatively), schizophrenia, attention-deficit/hyperactivity disorder, alcohol dependence, loneliness, anorexia nervosa, anxiety disorder, bipolar disorder, obsessive–compulsive disorder, and psychiatric disorders) and two physical diseases (cardiovascular disease and hypertensive disease). Conversely, MDD, SWB, and insomnia have a causal effect on neuroticism. We highlighted key genes contributing to the causal associations between neuroticism and MDD, including RBFOX1, RERE, SOX5, and TCF4, and those contributing to the causal associations between neuroticism and cardiovascular diseases, including MAD1L1, ARNTL, RERE, and SOX6. The present study indicates that genetic variation mediates the causal influences of neuroticism on mental health and cardiovascular diseases.

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Data availability

The present study was based on a secondary analysis of GWAS data and all data generated during the study are included in this published article.

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Acknowledgements

We thank members of the Psychiatric Genomics Consortium, 23andMe, the UKB, and other teams, who generously shared the GWAS data.

Funding

This work was supported by the National Key R&D Program of China (2016YFC1307000, 2020YFC2008002), and the Shanghai Key Laboratory of Psychotic Disorders (13dz2260500, 14-K06).

Author information

Author notes

  1. Fuquan Zhang, Ancha Baranova, and Chao Zhou contributed equally to this work.

Authors and Affiliations

  1. Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China

    Fuquan Zhang & Jiu Chen

  2. Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, 264 Guangzhou Road, Nanjing, 210029, China

    Fuquan Zhang

  3. School of Systems Biology, George Mason University, Manassas, 20110, USA

    Ancha Baranova & Hongbao Cao

  4. Research Centre for Medical Genetics, Moscow, 115478, Russia

    Ancha Baranova

  5. Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, 210029, China

    Chao Zhou & Xiangrong Zhang

  6. Institute of Brain Functional Imaging, Nanjing Medical University, Nanjing, 210029, China

    Jiu Chen

  7. Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200030, China

    Mingqing Xu

  8. Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University, Shanghai, 200030, China

    Mingqing Xu

Authors
  1. Fuquan Zhang
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  2. Ancha Baranova
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  3. Chao Zhou
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  4. Hongbao Cao
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  5. Jiu Chen
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  6. Xiangrong Zhang
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  7. Mingqing Xu
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Contributions

FZ and MX conceived and designed the study. FZ performed the data analysis and wrote the manuscript. FZ, AB, and MX revised the manuscript. CZ, XZ, JC, HC, and MX contributed to the data preparation and interpretation of the results. All the authors reviewed and approved the final version of the manuscript.

Corresponding authors

Correspondence to Fuquan Zhang or Mingqing Xu.

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The original online version of this article was revised due to corrections in the author contribution.

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Zhang, F., Baranova, A., Zhou, C. et al. Causal influences of neuroticism on mental health and cardiovascular disease. Hum Genet 140, 1267–1281 (2021). https://doi.org/10.1007/s00439-021-02288-x

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  • DOI: https://doi.org/10.1007/s00439-021-02288-x

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