論文

2020年12月

Rare genetic variants in the gene encoding histone lysine demethylase 4C (KDM4C) and their contributions to susceptibility to schizophrenia and autism spectrum disorder

Translational Psychiatry
  • Hidekazu Kato
  • Itaru Kushima
  • Daisuke Mori
  • Akira Yoshimi
  • Branko Aleksic
  • Yoshihiro Nawa
  • Miho Toyama
  • Sho Furuta
  • Yanjie Yu
  • Kanako Ishizuka
  • Hiroki Kimura
  • Yuko Arioka
  • Keita Tsujimura
  • Mako Morikawa
  • Takashi Okada
  • Toshiya Inada
  • Masahiro Nakatochi
  • Keiko Shinjo
  • Yutaka Kondo
  • Kozo Kaibuchi
  • Yasuko Funabiki
  • Ryo Kimura
  • Toshimitsu Suzuki
  • Kazuhiro Yamakawa
  • Masashi Ikeda
  • Nakao Iwata
  • Tsutomu Takahashi
  • Michio Suzuki
  • Yuko Okahisa
  • Manabu Takaki
  • Jun Egawa
  • Toshiyuki Someya
  • Norio Ozaki
  • 全て表示

10
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記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41398-020-01107-7
出版者・発行元
Springer Science and Business Media LLC

<title>Abstract</title>Dysregulation of epigenetic processes involving histone methylation induces neurodevelopmental impairments and has been implicated in schizophrenia (SCZ) and autism spectrum disorder (ASD). Variants in the gene encoding lysine demethylase 4C (<italic>KDM4C</italic>) have been suggested to confer a risk for such disorders. However, rare genetic variants in <italic>KDM4C</italic> have not been fully evaluated, and the functional impact of the variants has not been studied using patient-derived cells. In this study, we conducted copy number variant (CNV) analysis in a Japanese sample set (2605 SCZ and 1141 ASD cases, and 2310 controls). We found evidence for significant associations between CNVs in <italic>KDM4C</italic> and SCZ (<italic>p</italic> = 0.003) and ASD (<italic>p</italic> = 0.04). We also observed a significant association between deletions in <italic>KDM4C</italic> and SCZ (corrected <italic>p</italic> = 0.04). Next, to explore the contribution of single nucleotide variants in <italic>KDM4C</italic>, we sequenced the coding exons in a second sample set (370 SCZ and 192 ASD cases) and detected 18 rare missense variants, including p.D160N within the JmjC domain of KDM4C. We, then, performed association analysis for p.D160N in a third sample set (1751 SCZ and 377 ASD cases, and 2276 controls), but did not find a statistical association with these disorders. Immunoblotting analysis using lymphoblastoid cell lines from a case with <italic>KDM4C</italic> deletion revealed reduced KDM4C protein expression and altered histone methylation patterns. In conclusion, this study strengthens the evidence for associations between <italic>KDM4C</italic> CNVs and these two disorders and for their potential functional effect on histone methylation patterns.

リンク情報
DOI
https://doi.org/10.1038/s41398-020-01107-7
URL
http://www.nature.com/articles/s41398-020-01107-7.pdf
URL
http://www.nature.com/articles/s41398-020-01107-7
ID情報
  • DOI : 10.1038/s41398-020-01107-7
  • eISSN : 2158-3188

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