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Identifying common genome-wide risk genes for major psychiatric traits

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Abstract

Major psychiatric traits are genetically inter-correlated with one another, but it not well known which genes play pleiotropic effects across different traits. We curated and compared genes identified from large-scale genome-wide association studies for seven psychiatric traits, including depression, bipolar disorder, schizophrenia, autism spectrum disorder, attention-deficit/hyperactivity disorder, anxiety and neuroticism. We then explored biological functions of the top pleiotropic genes. A total of 243 cross-trait genes were identified for the seven traits. Except for autism spectrum disorder, there was significant enrichment of overlapped genes across these psychiatric traits. Chromosome 5q14.3, 11q23.2, and 7p22.3 are the three genomic regions conferring highest pleiotropic effects for these psychiatric traits. The long non-coding gene LINC00461 showed the highest pleiotropic effects on five psychiatric traits. In silico and functional studies with mice support the vital role of LINC00461 in neurodevelopment. In sum, our study provides insights into the shared genetic liability among major psychiatric traits.

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Acknowledgements

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

Funding

This work was supported by the National Natural Science Foundation of China No 81471364 (to FZ) and 81701326 (to SL) and Primary Research & Development Plan of Jiangsu Province No BE2016630 (to FZ).

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Author notes

  1. Sha Liu, Shuquan Rao, Yong Xu and Jun Li contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry, First Hospital/First Clinical Medical College of Shanxi Medical University, Taiyuan, 030001, China

    Sha Liu & Yong Xu

  2. School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610031, China

    Shuquan Rao

  3. Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, 100191, China

    Jun Li

  4. Key Laboratory of Mental Health, Ministry of Health and National Clinical Research Center for Mental Disorders (Peking University), Beijing, 100191, China

    Jun Li

  5. Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA

    Hailiang Huang

  6. Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA

    Hailiang Huang

  7. Key Laboratory for the Genetics of Development and Neuropsychiatric Disorders (Ministry of Education), Shanghai Key Laboratory of Psychotic Disorders, and Brain Science and Technology Research Center, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200240, China

    Xu Zhang

  8. Department of Anatomy and Embryology, School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, China

    Hui Fu

  9. Mental Health Center and Psychiatric Laboratory, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China

    Qiang Wang

  10. West China Brain Research Center, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China

    Qiang Wang

  11. School of Systems Biology, George Mason University (GMU), Fairfax, VA, 22030, USA

    Hongbao Cao & Ancha Baranova

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

    Ancha Baranova

  13. Wuxi Mental Health Center of Nanjing Medical University, Wuxi, 214151, China

    Chunhui Jin

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

    Fuquan Zhang

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  1. Sha Liu
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  2. Shuquan Rao
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  3. Yong Xu
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  4. Jun Li
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  5. Hailiang Huang
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  6. Xu Zhang
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  7. Hui Fu
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  8. Qiang Wang
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  9. Hongbao Cao
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  10. Ancha Baranova
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  11. Chunhui Jin
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  12. Fuquan Zhang
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Contributions

FZ and CJ conceived and designed the study. FZ, SL and SR performed the data analysis and manuscript writing. YX and JL conducted animal and functional experiments. HH, XZ, HF, QW, HC and AB contributed to manuscript preparation and interpretation of the results. All authors reviewed and approved the final version of the manuscript.

Corresponding author

Correspondence to Fuquan Zhang.

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Chunhui Jin and Fuquan Zhang: co-senior authors.

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Liu, S., Rao, S., Xu, Y. et al. Identifying common genome-wide risk genes for major psychiatric traits. Hum Genet 139, 185–198 (2020). https://doi.org/10.1007/s00439-019-02096-4

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