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Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population

Molecular Psychiatry volume 22, pages 954–960 (2017)Cite this article

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Abstract

Many schizophrenia susceptibility loci have been identified through genome-wide association studies (GWASs) in European populations. However, until recently, schizophrenia GWASs in non-European populations were limited to small sample sizes and have yielded few loci associated with schizophrenia. To identify genetic risk variations for schizophrenia in the Han Chinese population, we performed a two-stage GWAS of schizophrenia comprising 4384 cases and 5770 controls, followed by independent replications of 13 single-nucleotide polymorphisms in an additional 4339 schizophrenia cases and 7043 controls of Han Chinese ancestry. Furthermore, we conducted additional analyses based on the results in the discovery stage. The combined analysis confirmed evidence of genome-wide significant associations in the Han Chinese population for three loci, at 2p16.1 (rs1051061, in an exon of VRK2, P=1.14 × 10−12, odds ratio (OR)=1.17), 6p22.1 (rs115070292 in an intron of GABBR1, P=4.96 × 10−10, OR=0.77) and 10q24.32 (rs10883795 in an intron of AS3MT, P=7.94 × 10−10, OR=0.87; rs10883765 at an intron of ARL3, P=3.06 × 10−9, OR=0.87). The polygenic risk score based on Psychiatric Genomics Consortium schizophrenia GWAS data modestly predicted case–control status in the Chinese population (Nagelkerke R2: 1.7% ~5.7%). Our pathway analysis suggested that neurological biological pathways such as GABAergic signaling, dopaminergic signaling, cell adhesion molecules and myelination pathways are involved in schizophrenia. These findings provide new insights into the pathogenesis of schizophrenia in the Han Chinese population. Further studies are needed to establish the biological context and potential clinical utility of these findings.

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Acknowledgements

We express our sincere gratitude to all subjects who participated in the study. We acknowledge the schizophrenia working group of the Psychiatric GWAS Consortium (PGC) for making their results publicly available. This work was supported by grants from the National Key Technology R&D Program of China (2015BAI13B01), the National Natural Science Foundation of China (91232305, 81361120395, 91432304, 81571313) and the National High Technology Research and Development Program of China (2009AA022702).

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Author notes

  1. Members of Chinese Schizophrenia Collaboration Group are provided in the Supplementary Materials.

  2. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China

Authors and Affiliations

  1. Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China

    H Yu

  2. Department of Biochemistry, Institute of Mental Health, The Sixth Hospital, Peking University, Beijing, China

    H Yu, H Yan, J Li, Y Ma, L Mei, L Wang, T Lu, D Zhang & W Yue

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

    H Yu, H Yan, J Li, Y Ma, L Mei, L Wang, T Lu, D Zhang & W Yue

  4. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education) and the Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University, Shanghai, China

    Z Li, L Cai & Y Shi

  5. Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai, China

    Z Li & Y Shi

  6. Institute of Neuropsychiatric Science and Systems Biological Medicine, Shanghai Jiao Tong University, Shanghai, China

    Z Li & Y Shi

  7. The Affiliated Hospital of Qingdao University, Qingdao, China

    Z Li & Y Shi

  8. Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China

    X Zhang, B Liu & T Jiang

  9. National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China

    X Zhang, B Liu & T Jiang

  10. Department of Psychiatry, the University of Melbourne, Parkville, VIC, Australia

    C Liu

  11. Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China

    Q Wang & T Li

  12. State Key Laboratory of Biotherapy, Psychiatric laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, China

    Q Wang & T Li

  13. Department of Clinical Psychology, Wuxi Mental Health Center of Nanjing Medical University, Wuxi, China

    F Zhang

  14. Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan

    N Iwata & M Ikeda

  15. Department of Rheumatology and Immunology, Shanghai Changzheng Hospital, the Second Military Medical University, Shanghai, China

    M Li, H Xu & X Wu

  16. Tianjin Anding Hospital, Tianjin, China

    J Yang

  17. Hebei Mental Health Center, Baoding, Hebei, China

    K Li

  18. The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan, China

    L Lv

  19. Beijing Anding Hospital, Capital Medical University, Beijing, China

    X Ma & C Wang

  20. The Second Xiangya Hospital of Central South University, Changsha, China

    L Li

  21. Beijing HuiLongGuan Hospital, Peking University, Beijing, China

    F Yang

  22. Peking-Tsinghua Joint Center for Life Sciences/PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China

    D Zhang

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  1. H Yu
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Correspondence to W Yue.

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Yu, H., Yan, H., Li, J. et al. Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population. Mol Psychiatry 22, 954–960 (2017). https://doi.org/10.1038/mp.2016.212

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