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Implications of germline copy-number variations in psychiatric disorders: review of large-scale genetic studies

Journal of Human Genetics volume 66, pages 25–37 (2021)Cite this article

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Abstract

Copy number variants (CNVs), defined as genome sequences of ≥50 bp that differ in copy number from that in a reference genome, are a common form of structural variation. Germline CNVs account for some of the missing heritability that single nucleotide polymorphisms could not account for. Recent technological advances have had a huge impact on CNV research. Microarray technology enables relatively low-cost, high-throughput, genome-wide measurements, and short-read sequencing technology enables the detection of short CNVs that cannot be detected by microarrays. As a result, large-scale genetic studies have been able to identify a variety of common and rare germline CNVs and their associations with diseases. Rare germline CNVs have been reported to be associated with neuropsychiatric disorders. In this review, we focused on germline CNVs and briefly described their functional characteristics, formation mechanisms, detection methods, related databases, and the latest findings. Finally, we introduced recent large-scale genetic studies to assess associations of CNVs with diseases, especially psychiatric disorders, and discussed the use of CNV-based animal models to investigate the molecular and cellular mechanisms underlying these disorders. The development and implementation of improved detection methods, such as long-read single-molecule sequencing, are expected to provide additional insight into the molecular basis of psychiatric disorders and other complex diseases, thus facilitating basic and clinical research on CNVs.

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Acknowledgements

This work was supported in part by AMED under grant nos. JP20km0405216, JP20dm0107087, JP20dm0207075, JP20ak0101113, JP20dk0307075, JP20dk0307081, JP20dm0107160, and JP20ek0109411; and the Japan Society for the Promotion of Science (JSPS) KAKENHI grant nos. 17H05090, 15K19720, and 18H04040.

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  1. These authors contributed equally: Masahiro Nakatochi, Itaru Kushima

Authors and Affiliations

  1. Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, 461-8673, Japan

    Masahiro Nakatochi

  2. Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan

    Itaru Kushima & Norio Ozaki

  3. Medical Genomics Center, Nagoya University Hospital, Nagoya, Aichi, 466-8550, Japan

    Itaru Kushima & Norio Ozaki

Authors
  1. Masahiro Nakatochi
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  2. Itaru Kushima
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  3. Norio Ozaki
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Correspondence to Masahiro Nakatochi.

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Conflict of interest

NO has received research support and speakers’ honoraria from, or consulted for Sumitomo Dainippon, Otsuka, DAIICHI SANKYO, Tsumura, Nihon Medi-Physics, Pfizer, KAITEKI, Eli Lilly, Mochida, Eisai, Takeda, Novartis, Astellas, MSD, Meiji Seika Pharma, Janssen, Mitsubishi Tanabe, Kyowa, Taisho Pharma, EA Pharma, UCB and Shionogi, outside the submitted work. MN and IK declare no potential conflict of interest.

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Nakatochi, M., Kushima, I. & Ozaki, N. Implications of germline copy-number variations in psychiatric disorders: review of large-scale genetic studies. J Hum Genet 66, 25–37 (2021). https://doi.org/10.1038/s10038-020-00838-1

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  • DOI: https://doi.org/10.1038/s10038-020-00838-1

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