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An epigenome-wide methylation study of healthy individuals with or without depressive symptoms

  • Shimada, Mihoko1, 2
  • Otowa, Takeshi3
  • Miyagawa, Taku1, 2
  • Umekage, Tadashi4
  • Kawamura, Yoshiya5
  • Bundo, Miki6
  • Iwamoto, Kazuya6
  • Ikegame, Tempei7
  • Tochigi, Mamoru8
  • Kasai, Kiyoto7
  • Kaiya, Hisanobu9
  • Tanii, Hisashi10
  • Okazaki, Yuji11
  • Tokunaga, Katsushi2
  • Sasaki, Tsukasa12
  • 1 Tokyo Metropolitan Institute of Medical Science, Department of Psychiatry and Behavioral Sciences, Tokyo, Japan , Tokyo (Japan)
  • 2 The University of Tokyo, Department of Human Genetics, Graduate School of Medicine, Tokyo, Japan , Tokyo (Japan)
  • 3 Teikyo Heisei University, Graduate School of Clinical Psychology, Professional Degree Program in Clinical Psychology, Tokyo, Japan , Tokyo (Japan)
  • 4 The University of Tokyo, Division for Environment, Health and Safety, Tokyo, Japan , Tokyo (Japan)
  • 5 Shonan Kamakura General Hospital, Department of Psychiatry, Kanagawa, Japan , Kanagawa (Japan)
  • 6 Kumamoto University, Department of Molecular Brain Science, Graduate School of Medical Sciences, Kumamoto, Japan , Kumamoto (Japan)
  • 7 The University of Tokyo, Department of Neuropsychiatry, Graduate School of Medicine, Tokyo, Japan , Tokyo (Japan)
  • 8 Teikyo University School of Medicine, Department of Neuropsychiatry, Tokyo, Japan , Tokyo (Japan)
  • 9 Warakukai Med. Corp., Panic Disorder Research Center, Tokyo, Japan , Tokyo (Japan)
  • 10 Mie University, Department of Psychiatry, Institute of Medical Life Science, Graduate School of Medicine, Mie, Japan , Mie (Japan)
  • 11 Koseikai Michinoo Hospital, Department of Psychiatry, Nagasaki, Japan , Nagasaki (Japan)
  • 12 The University of Tokyo, Department of Physical and Health Education, Graduate School of Education, Tokyo, Japan , Tokyo (Japan)
Published Article
Journal of Human Genetics
Springer Nature
Publication Date
Jan 05, 2018
DOI: 10.1038/s10038-017-0382-y
Springer Nature


Major depressive disorder is a common psychiatric disorder that is thought to be triggered by both genetic and environmental factors. Depressive symptoms are an important public health problem and contribute to vulnerability to major depression. Although a substantial number of genetic and epigenetic studies have been performed to date, the detailed etiology of depression remains unclear and there are no validated biomarkers. DNA methylation is one of the major epigenetic modifications that play diverse roles in the etiology of complex diseases. In this study, we performed an epigenome-wide association study (EWAS) of DNA methylation on subjects with (N = 20) or without (N = 27) depressive symptoms in order to examine whether different levels of DNA methylation were associated with depressive tendencies. Employing methylation-array technology, a total of 363,887 methylation sites across the genomes were investigated and several candidate CpG sites associated with depressive symptoms were identified, especially annotated to genes linked to a G-protein coupled receptor protein signaling pathway. These data provide a strong impetus for validation studies using a larger cohort and support the possibility that G-protein coupled receptor protein signaling pathways are involved in the pathogenesis of depression.

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