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2017 Fiscal Year Annual Research Report

Elucidation of molecular mechanism of ADHD based on a prospective birth cohort study

Research Project

Project/Area Number 16K15352
Research InstitutionHokkaido University

Principal Investigator

岸 玲子  北海道大学, 環境健康科学研究教育センター, センター特別招へい教授 (80112449)

Co-Investigator(Kenkyū-buntansha) 荒木 敦子  北海道大学, 環境健康科学研究教育センター, 准教授 (00619885)
齊藤 卓弥  北海道大学, 医学研究院, 特任教授 (20246961)
三浦 りゅう  北海道大学, 環境健康科学研究教育センター, 特任助教 (20506414)
山崎 圭子  北海道大学, 環境健康科学研究教育センター, 特任講師 (60732120)
Project Period (FY) 2016-04-01 – 2018-03-31
Keywords環境疫学 / ADHD / エピジェネティクス / DNAメチル化 / 胎児期曝露
Outline of Annual Research Achievements

環境化学物質曝露によるADHD発症の胎児期マーカーとなるDNAメチル化部位(CpG部位)を探索するため、45万ヶ所CpG部位の網羅的解析を行った。前年度に行なった臍帯血DNA のエピゲノム網羅的解析ではgenomic inflationが起こり、偽陽性率が高くなっている可能性があったため、本年度は様々な統計手法を試み、inflationを最小に抑えた手法により、有機フッ素化合物、フタル酸エステル類、ビスフェノールA(BPA)、ダイオキシン・PCB類の胎児期曝露について、多重比較補正後もそれぞれの曝露濃度と統計学的に有意に関連するメチル変化を特定した。有機フッ素化合物については、隣接するいくつかのCpG部位でメチル化変化が同時に起こっている領域をも同定した。
メチル変化とADHDとの関連を検討するため、網羅的解析で明らかとなった曝露に起因するCpG部位の中から、神経系に分類される遺伝子のCpG部位、20か所を抽出し、6歳のADHD-RS調査票で見いだされたADHD疑い群(n=245)とコントロール群(n=317)の臍帯血DNAを用いて、次世代シークエンサーにより解析した。しかし、得られたメチル化率とADHD疑いとなるオッズとの有意な関連は認められなかった。この理由として、今回の次世代シーケンサーを用いたメチル化解析において、一定の信頼度を保っているかの指標となるカバレッジ数(各CpG部位配列を重ねて読んだ回数)が十分に取得できなかったこと、サンプル間でカバレッジ数がばらついてしまい外れ値が多くなってしまったことが原因の1つと考えられ、現在、再解析を行っている。また、選択したCpG部位が妥当でなかったことも考えられ、今後、解析するCpG部位の再検討が必要と考えている。

  • Research Products

    (25 results)

All 2018 2017

All Journal Article (19 results) (of which Peer Reviewed: 19 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Association between DNA methylation in cord blood and maternal smoking: The Hokkaido Study on Environment and Children’s Health2018

    • Author(s)
      K. Miyake, A. Kawaguchi, R. Miura, Sa. Kobayashi, N. Q. Vuong Tran, Su. Kobayashi, C. Miyashita, A. Araki, T. Kubota, Z. Yamagata, R. Kishi
    • Journal Title

      Scientific Report

      Volume: 8 Pages: 5654

    • DOI

      10.1038/s41598-018-23772-x

    • Peer Reviewed
  • [Journal Article] Prenatal organochlorine pesticide exposure and the disruption of steroids and reproductive hormones in cord blood: The Hokkaido study2018

    • Author(s)
      Araki Atsuko、Miyashita Chihiro、Mitsui Takahiko、Goudarzi Houman、Mizutani Futoshi、Chisaki Youichi、Itoh Sachiko、Sasaki Seiko、Cho Kazutoshi、Moriya Kimihiko、Shinohara Nobuo、Nonomura Katsuya、Kishi Reiko
    • Journal Title

      Environment International

      Volume: 110 Pages: 1~13

    • DOI

      https://doi.org/10.1016/j.envint.2017.10.006

    • Peer Reviewed
  • [Journal Article] Association of prenatal exposure to PCDD/Fs and PCBs with maternal and infant thyroid hormones: The Hokkaido Study on Environment and Children's Health2018

    • Author(s)
      Baba Toshiaki、Ito Sachiko、Yuasa Motoyuki、Yoshioka Eiji、Miyashita Chihiro、Araki Atsuko、Sasaki Seiko、Kobayashi Sumitaka、Kajiwara Jumboku、Hori Tsuguhide、Kato Shizue、Kishi Reiko
    • Journal Title

      Science of The Total Environment

      Volume: 615 Pages: 1239~1246

    • DOI

      https://doi.org/10.1016/j.scitotenv.2017.09.038

    • Peer Reviewed
  • [Journal Article] Effects of low-level prenatal exposure to dioxins on cognitive development in Japanese children at 42 months2018

    • Author(s)
      Ikeno Tamiko、Miyashita Chihiro、Nakajima Sonomi、Kobayashi Sumitaka、Yamazaki Keiko、Saijo Yasuaki、Kita Toshiko、Sasaki Seiko、Konishi Kanae、Kajiwara Junboku、Hori Tsuguhide、Kishi Reiko
    • Journal Title

      Sci Total Environ.

      Volume: 618 Pages: 1423~1430

    • DOI

      10.1016/j.scitotenv.2017.09.267

    • Peer Reviewed
  • [Journal Article] Birth cohorts in Asia: The importance, advantages, and disadvantages of different-sized cohorts2018

    • Author(s)
      Kishi Reiko、Araki Atsuko、Minatoya Machiko、Itoh Sachiko、Goudarzi Houman、Miyashita Chihiro
    • Journal Title

      Science of The Total Environment

      Volume: 615 Pages: 1143~1154

    • DOI

      https://doi.org/10.1016/j.scitotenv.2017.08.268

    • Peer Reviewed / Open Access
  • [Journal Article] Association between Fetal Adipokines and Child Behavioral Problems at Preschool Age: The Hokkaido Study on Environment and Children’s Health2018

    • Author(s)
      Minatoya Machiko、Itoh Sachiko、Araki Atsuko、Tamura Naomi、Yamazaki Keiko、Miyashita Chihiro、Kishi Reiko
    • Journal Title

      Int. J. Environ. Res. Public Health

      Volume: 15 Pages: 120~120

    • DOI

      10.3390/ijerph15010120

    • Peer Reviewed
  • [Journal Article] An epigenome-wide study of cord blood DNA methylations in relation to prenatal perfluoroalkyl substance exposure: The Hokkaido study2018

    • Author(s)
      Miura Ryu、Araki Atsuko、Miyashita Chihiro、Kobayashi Sumitaka、Kobayashi Sachiko、Wang Shu-Li、Chen Chung-Hsing、Miyake Kunio、Ishizuka Mayumi、Iwasaki Yusuke、Ito Yoichi M.、Kubota Takeo、Kishi Reiko
    • Journal Title

      Environment International

      Volume: 115 Pages: 21~28

    • DOI

      https://doi.org/10.1016/j.envint.2018.03.004

    • Peer Reviewed
  • [Journal Article] 「2万人規模の出生コーホートと,500人規模の小コーホートからなる北海道スタディが目指してきたもの:環境と子どもの健康―先天異常・発達・アレルギーの15年におよぶ経験と成果」2018

    • Author(s)
      岸玲子,荒木敦子,宮下ちひろ,伊藤佐智子,湊屋街子,小林澄貴,山﨑圭子,アイツバマイゆふ,三浦りゅう,田村菜穂美
    • Journal Title

      日本衛生学雑誌

      Volume: - Pages: -

    • Peer Reviewed
  • [Journal Article] Association between prenatal exposure to organochlorine pesticides and the mental and psychomotor development of infants at ages 6 and 18 months: The Hokkaido Study on Environment and Children’s Health2017

    • Author(s)
      Yamazaki Keiko、Araki Atsuko、Nakajima Sonomi、Miyashita Chihiro、Ikeno Tamiko、Itoh Sachiko、Minatoya Machiko、Kobayashi Sumitaka、Mizutani Futoshi、Chisaki Yoichi、Kishi Reiko
    • Journal Title

      NeuroToxicology

      Volume: 印刷中 Pages: -

    • DOI

      10.1016/j.neuro.2017.11.011

    • Peer Reviewed
  • [Journal Article] Prenatal di(2-ethylhexyl) phthalate exposure and disruption of adrenal androgens and glucocorticoids levels in cord blood: The Hokkaido Study2017

    • Author(s)
      Araki Atsuko、Mitsui Takahiko、Goudarzi Houman、Nakajima Tamie、Miyashita Chihiro、Itoh Sachiko、Sasaki Seiko、Cho Kazutoshi、Moriya Kimihiko、Shinohara Nobuo、Nonomura Katsuya、Kishi Reiko
    • Journal Title

      Sci Total Environ.

      Volume: 581-582 Pages: 297~304

    • DOI

      10.1016/j.scitotenv.2016.12.124

    • Peer Reviewed
  • [Journal Article] The Association of Prenatal Exposure to Perfluorinated Chemicals with Glucocorticoid and Androgenic Hormones in Cord Blood Samples: The Hokkaido Study2017

    • Author(s)
      Goudarzi H., Araki A., Itoh S., Sasaki S., Miyashita C., Mitsui T., Nakazawa H., Nonomura K., Kishi R.
    • Journal Title

      Environ Health Perspect

      Volume: 125 Pages: 111-118

    • DOI

      10.1289/EHP142

    • Peer Reviewed
  • [Journal Article] The Hokkaido Birth Cohort Study on Environment and Children’s Health: cohort profile-updated 20172017

    • Author(s)
      R. Kishi, A. Araki, M. Minatoya, T. Hanaoka, C. Miyashita, S. Itoh, S. Kobayashi, Y. Ait Bamai, K. Yamazaki, R. Miura, N. Tamura, K. Ito. H. Goudarzi
    • Journal Title

      Environmental Health and Preventive Medicine

      Volume: - Pages: 22-46

    • DOI

      10.1186/s12199-017-0654-3

    • Peer Reviewed / Open Access
  • [Journal Article] Effects of prenatal perfluoroalkyl acid exposure on cord blood IGF2/H19 methylation and ponderal index: the Hokkaido study2017

    • Author(s)
      S. Kobayashi, K. Azumi, H. Goudarzi, A. Araki, C. Miyashita, S. Kobayashi, S. Itoh, S. Sasaki, M. Ishizuka, H. Nakazawa, T. Ikeno, R. Kishi
    • Journal Title

      Journal of Exposure Science and Environmental Epidemiology

      Volume: 27 Pages: 251-259

    • Peer Reviewed
  • [Journal Article] Gender-specific association of exposure to non-dioxin-like polychlorinated biphenyls during pregnancy with methylation levels of H19 and long interspersed nuclear element-1 in cord blood in the Hokkaido study2017

    • Author(s)
      Kobayashi Sumitaka、Sata Fumihiro、Miyashita Chihiro、Miura Ryu、Azumi Kaoru、Kobayashi Sachiko、Goudarzi Houman、Araki Atsuko、Ishizuka Mayumi、Todaka Takashi、Kajiwara Jumboku、Hori Tsuguhide、Kishi Reiko
    • Journal Title

      Toxicology

      Volume: 390 Pages: 135~145

    • DOI

      10.1016/j.tox.2017.08.010

    • Peer Reviewed
  • [Journal Article] Prenatal di-2-ethylhexyl phthalate exposure and cord blood adipokine levels and birth size: The Hokkaido study on environment and children's health2017

    • Author(s)
      Minatoya Machiko、Araki Atsuko、Miyashita Chihiro、Sasaki Seiko、Goto Yuko、Nakajima Tamie、Kishi Reiko
    • Journal Title

      Sci Total Environ

      Volume: 579 Pages: 606~611

    • DOI

      10.1016/j.scitotenv.2016.11.051

    • Peer Reviewed
  • [Journal Article] Cord blood BPA level and child neurodevelopment and behavioral problems: The Hokkaido Study on Environment and Children's Health2017

    • Author(s)
      Minatoya Machiko、Araki Atsuko、Nakajima Sonomi、Sasaki Seiko、Miyashita Chihiro、Yamazaki Keiko、Yamamoto Jun、Matumura Toru、Kishi Reiko
    • Journal Title

      Sci Total Environ

      Volume: 607-608 Pages: 351~356

    • DOI

      10.1016/j.scitotenv.2017.06.060

    • Peer Reviewed
  • [Journal Article] Association of prenatal exposure to perfluoroalkyl substances with cord blood adipokines and birth size: The Hokkaido Study on environment and children's health2017

    • Author(s)
      Minatoya Machiko、Itoh Sachiko、Miyashita Chihiro、Araki Atsuko、Sasaki Seiko、Miura Ryu、Goudarzi Houman、Iwasaki Yusuke、Kishi Reiko
    • Journal Title

      Environ Res

      Volume: 156 Pages: 175~182

    • DOI

      10.1016/j.envres.2017.03.033

    • Peer Reviewed
  • [Journal Article] Cord Blood Bisphenol A Levels and Reproductive and Thyroid Hormone Levels of Neonates: The Hokkaido Study on Environment and Children's Health2017

    • Author(s)
      M. Minatoya, S. Sasaki, A. Araki, C. Miyashita, S. Itoh, J. Yamamoto, T. Matsumura, T. Mitsui, K. Moriya, K. Cho, K. Morioka, H. Minakami, N. Shinohara, R. Kishi
    • Journal Title

      Epidemiology

      Volume: 1 Pages: S3-S9

    • DOI

      10.1097/EDE.0000000000000716

    • Peer Reviewed
  • [Journal Article] Sex-specific differences in effect of prenatal exposure to dioxin-like compounds on neurodevelopment in Japanese children: Sapporo cohort study2017

    • Author(s)
      Nakajima Sonomi、Saijo Yasuaki、Miyashita Chihiro、Ikeno Tamiko、Sasaki Seiko、Kajiwara Junboku、Kishi Reiko
    • Journal Title

      Environmental Research

      Volume: 159 Pages: 222~231

    • DOI

      https://doi.org/10.1016/j.envres.2017.08.006

    • Peer Reviewed
  • [Presentation] 胎児期の有機塩素系農薬曝露が3.5 歳の児の知的機能に及ぼす影響- 北海道スタディ2018

    • Author(s)
      山﨑圭子, 荒木敦子, 中島そのみ, 宮下ちひろ, 池野多美子, 伊藤佐智子, 湊屋街子, 水谷太, 苣木洋一, 岸玲子
    • Organizer
      第88回日本衛生学会学術総会
  • [Presentation] 胎児期の両親の喫煙と幼児期におけるADHD 症状の関連2018

    • Author(s)
      湊屋街子, 伊藤佐智子, 小林澄貴, 山﨑圭子, 宮下ちひろ, 荒木敦子, 岸玲子
    • Organizer
      第88回日本衛生学会学術総会
  • [Presentation] 胎児期のPCB 類曝露による児のH19・LINE-1のDNA メチル化への影響:北海道スタディ2018

    • Author(s)
      小林澄貴, 佐田文宏, 宮下ちひろ, 三浦りゅう, ゴウダルジ・ホウマヌ, 荒木敦子, 梶原淳睦, 堀就英, 岸玲子
    • Organizer
      第88回日本衛生学会学術総会
  • [Presentation] Exposure to bisphenol A and phthalates during pregnancy and child neurobehavioral development at preschool age: The Hokkaido Study2017

    • Author(s)
      Minatoya M., Itoh S., Miyashita C., Araki A., Tamura N., Yamamoto J., Onoda Y., Matsumura T., Kishi R.
    • Organizer
      The 29th Annual Scientific Conference of the International Society of Environmental Epidemiology (ISEE) 2017
    • Int'l Joint Research
  • [Presentation] 臍帯血アディポカイン濃度と子どもの発達:環境と子どもの健康に関する北海道スタディ2017

    • Author(s)
      湊屋街子, 小林澄貴, 須山聡, 岸玲子
    • Organizer
      第76回日本公衆衛生学会
  • [Presentation] 胎児期PCB・Dioxin曝露が学童期の脳活動に与える影響についての検討2017

    • Author(s)
      山﨑圭子, 岸玲子
    • Organizer
      第35回日本生理心理学会

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Published: 2018-12-17  

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