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Genetic evidence for association between NOTCH4 and schizophrenia supported by a GWAS follow-up study in a Japanese population

Molecular Psychiatry volume 18, pages 636–638 (2013)Cite this article

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Using stringent criteria, we followed-up a genome-wide association study (GWAS) finding1 to examine the involvement of the developmental regulatory gene NOTCH4 in schizophrenia. This is the first study in a Japanese population that satisfies genome-wide significance between a particular single-nucleotide polymorphism (SNP) and schizophrenia.

The past 5 years have seen significant genetic discoveries made through GWASs. Although in schizophrenia the effect sizes have been relatively small (odds ratio (OR) of <1.2), these studies collectively provide strong evidence for association of a number of susceptibility genes. The major loci identified for schizophrenia risk are located in the major histocompatibility complex region in 6p21.3–p22.1. The Psychiatric GWAS Consortium, a sample consisting mainly of Caucasian subjects, reported 136 SNPs with genome-wide significance (5 × 10−8), and among them 129 SNPs were located from 25 to 33 Mb at chromosome 6.2 In addition, a recent Asian GWAS from a Chinese population showed a stringent level of significance at ZKSCAN4 (chr6: 28.32 Mb),3 even though another larger Chinese population GWAS4 and our prior Japanese population-based GWAS (total sample size: 1108)1 did not detect any genome-wide significance in this region. In our previous study,1 however, only one signal within these loci maximized at a SNP (rs2071287: chr6: 32 170 433 bp on hg19) in NOTCH4 (chr6: 32.16 to 32.19 Mb). To provide a more complete analysis, in the current study, we expanded the sample size to verify whether this SNP (rs2071287: C>T) in NOTCH4 shows strong support for genetic association.

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Acknowledgements

This work was supported by research grants from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan; Ministry of Health, Labor and Welfare of Japan; Academic Frontier Project for Private Universities, Comparative Cognitive Science Institutes; Core Research for Evolutional Science and Technology; Uehara Memorial Foundation; SENSHIN Medical Research Foundation; Takeda Science Foundation; Novaltis Foundation, Japan; Strategic Research Program for Brain Sciences of the MEXT of Japan.

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Authors and Affiliations

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

    M Ikeda, Y Fukuo, T Okochi & N Iwata

  2. Japan Science and Technology Agency, The Core Research for Evolutional Science and Technology, Kawaguchi, Japan

    M Ikeda, B Aleksic, Y Fukuo, T Okochi, N Ozaki & N Iwata

  3. Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan

    B Aleksic & N Ozaki

  4. Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama, Japan

    K Yamada, Y Iwayama-Shigeno, T Toyota, E Hattori & T Yoshikawa

  5. Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan

    K Matsuo & H Tanaka

  6. Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan

    S Numata & T Ohmori

  7. Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Y Watanabe, A Nunokawa & T Someya

  8. Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan

    T Ohnuma, N Shibata & H Arai

  9. Department of Neuropsychiatry, Osaka Medical College, Osaka, Japan

    T Kaneko & H Yoneda

  10. Department of Neuropsychiatry, Kochi Medical School, Kochi, Japan

    S Shimodera

  11. Division of Genetic Information, Institute for Genome Research, The University of Tokushima Graduate School of Medicine, Tokushima, Japan

    M Itakura

Authors
  1. M Ikeda
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  2. B Aleksic
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  3. K Yamada
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  4. Y Iwayama-Shigeno
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  6. S Numata
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  7. Y Watanabe
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  8. T Ohnuma
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  9. T Kaneko
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  11. T Okochi
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  12. T Toyota
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  13. E Hattori
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  14. S Shimodera
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  15. M Itakura
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  16. A Nunokawa
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  17. N Shibata
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  18. H Tanaka
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  19. H Yoneda
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  20. H Arai
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  21. T Someya
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  22. T Ohmori
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  23. T Yoshikawa
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  24. N Ozaki
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  25. N Iwata
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Corresponding author

Correspondence to N Iwata.

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Ikeda, M., Aleksic, B., Yamada, K. et al. Genetic evidence for association between NOTCH4 and schizophrenia supported by a GWAS follow-up study in a Japanese population. Mol Psychiatry 18, 636–638 (2013). https://doi.org/10.1038/mp.2012.74

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