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

Research Project

Project/Area Number 16K15352
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Epidemiology and preventive medicine
Research InstitutionHokkaido University

Principal Investigator

Reiko kishi  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)
Research Collaborator AIT BAMAI Yu  北海道大学, 環境健康科学研究教育センター, 特任講師 (90752907)
KOBAYASHI Sumitaka  北海道大学, 環境健康科学研究教育センター, 特任講師 (10733371)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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 Final Research Achievements

We targeted DNA methylation as a mediator between prenatal exposure to environmental chemicals and attention-deficit/hyperactivity disorder (ADHD). We assessed methylation levels at 450K cytosine-guanine dinucleotide sites (CpGs) in cord blood DNA using an Illumina HumanMethylation 450 BeadChip, and examined association between methylation and prenatal exposure to perfluoroalkyl substances, phthalates, and bisphenol A. The epigenome-wide analyses (EWAS) showed significant differences in methylation associated with prenatal exposure.
To investigate prospective association between DNA methylation at birth and ADHD-related behavior at 6 years, we extracted DNA from cord blood of ADHD groups (n=245) identified with ADHD rating scale (ADHD-RS) and control groups (n=317). Using a next-generation sequencer, we have quantified methylation levels at CpGs that showed significant association with prenatal exposure in the EWAS.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (38 results)

All 2018 2017 2016

All Journal Article (25 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 24 results,  Open Access: 16 results,  Acknowledgement Compliant: 6 results) Presentation (13 results) (of which Int'l Joint Research: 7 results,  Invited: 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)
      Miyake Kunio、Kawaguchi Akio、Miura Ryu、Kobayashi Sachiko、Tran Nguyen Quoc Vuong、Kobayashi Sumitaka、Miyashita Chihiro、Araki Atsuko、Kubota Takeo、Yamagata Zentaro、Kishi Reiko
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 5654-5654

    • DOI

      10.1038/s41598-018-23772-x

    • NAID

      120006533154

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [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

      The Hokkaido study. Environ Int.

      Volume: 110 Pages: 1-13

    • DOI

      10.1016/j.envint.2017.10.006

    • NAID

      120006776798

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [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

      10.1016/j.scitotenv.2017.09.038

    • NAID

      120006796030

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [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

      Science of The Total Environment

      Volume: 618 Pages: 1423-1430

    • DOI

      10.1016/j.scitotenv.2017.09.267

    • NAID

      120006812530

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [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

      10.1016/j.scitotenv.2017.08.268

    • NAID

      120006796031

    • Related Report
      2017 Annual Research Report
    • 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 Issue: 1 Pages: 120-120

    • DOI

      10.3390/ijerph15010120

    • NAID

      120006459317

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [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

      10.1016/j.envint.2018.03.004

    • NAID

      120006847752

    • Related Report
      2017 Annual Research Report
    • 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: -

    • NAID

      130007378561

    • Related Report
      2017 Annual Research Report
    • 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: 201-208

    • DOI

      10.1016/j.neuro.2017.11.011

    • NAID

      120006769937

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 A., Mitsui T., Goudarzi H., Nakajima T., Miyashita C., Itoh S., Sasaki S., Cho K., Moriya K., Shinohara N., Nonomura K., Kishi R.
    • Journal Title

      Science of the Total Environment

      Volume: 581-582 Pages: 297-304

    • DOI

      10.1016/j.scitotenv.2016.12.124

    • NAID

      120006558980

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The Association of Prenatal Exposure to Perfluorinated Chemicals with Glucocorticoid and Androgenic Hormones in Cord Blood Samples: The Hokkaido Study.2017

    • 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 Issue: 1 Pages: 111-118

    • DOI

      10.1289/ehp142

    • NAID

      120006533152

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Hokkaido Birth Cohort Study on Environment and Children’s Health: cohort profile―updated 20172017

    • Author(s)
      Kishi Reiko、the members of The Hokkaido Study on Environment and Children’s Health、Araki Atsuko、Minatoya Machiko、Hanaoka Tomoyuki、Miyashita Chihiro、Itoh Sachiko、Kobayashi Sumitaka、Ait Bamai Yu、Yamazaki Keiko、Miura Ryu、Tamura Naomi、Ito Kumiko、Goudarzi Houman
    • Journal Title

      Environ Health Prev Med

      Volume: 22 Issue: 1 Pages: 22-46

    • DOI

      10.1186/s12199-017-0654-3

    • NAID

      120006337770

    • Related Report
      2017 Annual Research Report
    • 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

    • NAID

      120006220016

    • Related Report
      2017 Annual Research Report
    • 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

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 M., Araki A., Miyashita C., Sasaki S., Goto Y., Nakajima T., Kishi R.
    • Journal Title

      Sci Total Environ

      Volume: 579 Pages: 606-611

    • DOI

      10.1016/j.scitotenv.2016.11.051

    • NAID

      120006551571

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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

      Science of The Total Environment

      Volume: 607-608 Pages: 351-356

    • DOI

      10.1016/j.scitotenv.2017.06.060

    • NAID

      120006776797

    • Related Report
      2017 Annual Research Report
    • 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 health.2017

    • Author(s)
      Minatoya M, Itoh S, Miyashita C, Araki A, Sasaki S, Miura R, Goudarzi H, Iwasaki Y, Kishi R.
    • Journal Title

      Environ Res

      Volume: 156 Pages: 175-182

    • DOI

      10.1016/j.envres.2017.03.033

    • NAID

      120006649167

    • Related Report
      2017 Annual Research Report
    • 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 Health.2017

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

      Epidemiology.

      Volume: - Pages: S3-S9

    • DOI

      10.1097/ede.0000000000000716

    • NAID

      120006536947

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [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

      10.1016/j.envres.2017.08.006

    • NAID

      120006734154

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of prenatal perfluoroalkyl acid exposure on cord blood IGF2/H19 methylation and ponderal index: the Hokkaido study2017

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

      Journal of Exposure Science and Environmental Epidemiology

      Volume: -

    • NAID

      120006220016

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Associated factors of behavioural problems in children at preschool age: the Hokkaido study on environment and children's health2016

    • Author(s)
      Minatoya M., Itoh S., Araki A., Tamura N., Yamazaki K., Nishihara S., Miyashita C., Kishi R.
    • Journal Title

      Child Care Health Dev.

      Volume: - Issue: 3 Pages: 1365-2214

    • DOI

      10.1111/cch.12424

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Prenatal exposure to perfluorinated chemicals and neurodevelopment in early infancy: The Hokkaido Study2016

    • Author(s)
      H. Goudarzi, S. Nakajima, T. Ikeno, S. Sasaki, S. Kobayashi, C. Miyashita, S. Ito, A. Araki, H. Nakazawa and R. Kishi
    • Journal Title

      Sci Total Environ

      Volume: 541 Pages: 1002-1010

    • DOI

      10.1016/j.scitotenv.2015.10.017

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 【講座 子どもを取り巻く環境と健康】第15回 ダイオキシン類曝露と児の神経発達2016

    • Author(s)
      中島そのみ, 岸玲子
    • Journal Title

      公衆衛生

      Volume: 80(5) Pages: 371-378

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 【講座 子どもを取り巻く環境と健康】第16回 ADHD(注意欠如・多動性障害)とASD(自閉スペクトラム症)2016

    • Author(s)
      池野多美子, 小林澄貴, 山崎圭子, 西原進吉, 岸玲子
    • Journal Title

      公衆衛生

      Volume: 80(6) Pages: 445-450

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 【講座 子どもを取り巻く環境と健康】第17回 胎児期の化学物質曝露による後天的な遺伝子発現制御への影響2016

    • Author(s)
      宮下ちひろ, 小林祥子, 岸玲子
    • Journal Title

      公衆衛生

      Volume: 80(7) Pages: 531-537

    • Related Report
      2016 Research-status Report
  • [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
    • Related Report
      2017 Annual Research Report
  • [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
    • Related Report
      2017 Annual Research Report
  • [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
    • Related Report
      2017 Annual Research Report
  • [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
    • Related Report
      2017 Annual Research Report
    • 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
    • Related Report
      2017 Annual Research Report
  • [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
    • Related Report
      2017 Annual Research Report
  • [Presentation] Identification of Risks of Endocrine Disrupting Chemicals Based on Early Life Exposure Assessment: The Hokkaido Study2016

    • Author(s)
      Kishi, R.
    • Organizer
      International Frontier Forums of Reproductive Medicine and 2016 International Symposium on Construction and Application of Birth Cohort
    • Place of Presentation
      Nanjing Medical University, Nanjing, China
    • Year and Date
      2016-11-19
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Environmental endocrine-disrupting chemicals and their effects to children: 13 years progress of the Hokkaido Birth Cohort Study2016

    • Author(s)
      Kishi, R.
    • Organizer
      PPTOX V.
    • Place of Presentation
      Kitakyushu International Conference Center, Kitakyushu, Japan
    • Year and Date
      2016-11-13
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] ssociated prenatal factors of behavioral and emotional problems in 5 year-old children: The Hokkaido Study2016

    • Author(s)
      Minatoya M., Tamura N., Ito S., Miyashita C., Araki A., Kishi R.
    • Organizer
      ISEE2016: 28th Annual Conference International Society for Environmental Epidemiology
    • Place of Presentation
      Auditorium Parco della Musica, Itaty, Roma
    • Year and Date
      2016-09-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Prenatal environment and child behavioral and coordination development at preschool age in the Hokkaido Study2016

    • Author(s)
      Minatoya M., Tamura N., Itoh S., Suyama S., Miyashita C., Araki A., Saito T., Nakai A., Kishi R.
    • Organizer
      ISEE-ISES AC2016
    • Place of Presentation
      Sapporo, Hokkaido, Japan
    • Year and Date
      2016-06-26
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Epigenome-wide Pathway Analyses of Prenatal Perfluoroalkyl Acids Exposure on Cord Blood DNA Methylation: The Hokkaido Study2016

    • Author(s)
      Kobayashi S., Miura R., Miyashita C., Araki A., Ishizuka M., Nakazawa H., Ito Y. M., Kubota T., Kishi R.
    • Organizer
      ISEE-ISES AC2016
    • Place of Presentation
      Sapporo, Hokkaido, Japan
    • Year and Date
      2016-06-26
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Epigenome-wide analyses of prenatal perfluoroalkyl acids exposure on cord blood DNA methylation: the Hokkaido study2016

    • Author(s)
      Kobayashi S., Miura R., Miyashita C., Araki A., Ishizuka M., Nakazawa H., Ito Y., Kubota T., Kishi R.
    • Organizer
      ISEE-ISES AC2016
    • Place of Presentation
      Sapporo, Hokkaido, Japan
    • Year and Date
      2016-06-26
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 臍帯血中ビスフェノールA濃度と子どもの行動発達:北海道スタディ2016

    • Author(s)
      3.湊屋街子, 佐々木成子, 中島そのみ, 山本潤, 松村徹, 宮下ちひろ, 荒木敦子, 岸玲子
    • Organizer
      第86回日本衛生学会
    • Place of Presentation
      旭川市民文化会館(北海道・旭川市)
    • Year and Date
      2016-05-11
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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