Genome-wide analysis of copy number variations in individual differences in vulnerability to and severity of substance dependence regarding nicotine and other addictive substances
Project/Area Number |
17K08970
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Applied pharmacology
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Research Institution | Tokyo Metropolitan Institute of Medical Science |
Principal Investigator |
NISHIZAWA Daisuke 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 主席研究員 (80450584)
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Co-Investigator(Kenkyū-buntansha) |
池田 和隆 公益財団法人東京都医学総合研究所, 精神行動医学研究分野, 分野長 (60281656)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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Keywords | ニコチン / 物質依存脆弱性・重症度 / ゲノムワイド関連解析 / コピー数多型・変異 / ニコチン依存 / 物質依存脆弱性 / 物質依存 / 個別化医療 |
Outline of Final Research Achievements |
We comprehensively explored genetic contributors of copy number variations (CNVs) to smoking behavior, particularly nicotine dependence, in a total of 300, followed by 240 and 192, Japanese patients. A genome-wide CNV study was conducted for the genotype data obtained by whole-genome genotyping with SNP arrays approximately targeting over 300,000 markers. From among several smoking-related traits, the Fagerström Test for Nicotine Dependence (FTND), the Tobacco Dependence Screener (TDS), and the numbers of cigarettes smoked per day (CPD), were analyzed. In genome-wide analyses, several CNVs were selected to be possibly associated with these traits. Among them, a ~20 kbp CNV mapped at 22q13.1, which is located in the region of the APOBEC3B gene, and a ~3 kbp CNV mapped at 17q12, which is located at the neighboring region of the PLXDC1 gene, showed genome-wide significant association with FTND score in the initial 300 samples and TDS score in the following 192 samples, respectively.
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Academic Significance and Societal Importance of the Research Achievements |
さらに統計学的に信頼性の高い結果を得るためにも、今後別途追加検体を用いてのさらなる再現性検証研究が必要とされるが、本研究において同定されたAPOBEC3B遺伝子領域の約20kbpのコピー数変異・多型(CNV)及びPLXDC1遺伝子領域近傍の約3kbpのCNV等の有力候補CNVは、他集団と共通、並びに日本人に特有の喫煙行動に寄与する遺伝要因の発見に役立つ可能性が示唆された。
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Report
(4 results)
Research Products
(73 results)
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[Journal Article] Polygenetic risk scores for major psychiatric disorders among schizophrenia patients, their first-degree relatives, and healthy participants.2020
Author(s)
Ohi K, Nishizawa D, Shimada T, Kataoka Y, Hasegawa J, Shioiri T, Kawasaki Y, Hashimoto R, Ikeda K
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Journal Title
Int J Neuropsychopharmacol
Volume: 23
Issue: 3
Pages: 157-164
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Taxane-induced sensory peripheral neuropathy is associated with an SCN9A single nucleotide polymorphism in Japanese patients.2020
Author(s)
Tanabe Y, Shiraishi S, Hashimoto K, Ikeda K, Nishizawa D, Hasegawa J, Shimomura A, Ozaki Y, Tamura N, Yunokawa M, Yonemori K, Takano T, Kawabata H, Tamura K, Fujiwara Y, Shimizu C
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Journal Title
BMC Cancer
Volume: 20
Issue: 1
Pages: 325-325
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Adiponectin receptor 1 gene is potentially associated with severity of postoperative pain but not cancer pain.2020
Author(s)
Ninagawa J, Sumitani M, Nishizawa D, Nagashima M, Mietani K, Abe H, Inoue R, Hozumi J, Tsuchida R, Ikeda K, Yamada Y
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Journal Title
Medicine
Volume: 99
Issue: 5
Pages: e18924-e18924
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Gamma-aminobutyric acid transaminase genetic polymorphism is a candidate locus for responsiveness to opioid analgesics in patients with cancer pain: an exploratory study2018
Author(s)
Yokoshima Y, Sumitani M, Nishizawa D, Nagashima M, Ikeda K, Kato R, Hozumi J, Abe H, Azuma K, Tsuchida R, Yamada Y, Japanese TR-Cancer Pain research Group
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Journal Title
Neuropsychopharmacol Rep
Volume: 38(4)
Issue: 4
Pages: 175-181
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Association between the rs7583431 single-nucleotide polymorphism close to the activating transcription factor 2 (ATF2) gene and the analgesic effect of fentanyl in the cold pain test.2018
Author(s)
Aoki Y, Nishizawa D, Yoshida K, Hasegawa J, Kasai S, Takahashi K, Koukita Y, Ichinohe T, Hayashida M, Fukuda K, Ikeda K
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Journal Title
Neuropsychopharmacology Rep
Volume: 印刷中
Issue: 2
Pages: 86-91
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Genome-wide scan identifies candidate loci related to remifentanil requirements during laparoscopic-assisted colectomy.2018
Author(s)
2.Nishizawa D, Mieda T, Tsujita M, Nakagawa H, Yamaguchi S, Kasai S, Hasegawa J, Fukuda KI, Kitamura A, Hayashida M, Ikeda K.
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Journal Title
Pharmacogenomics
Volume: 19
Issue: 2
Pages: 113-127
DOI
Related Report
Peer Reviewed
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[Journal Article] Paclitaxel-induced sensory peripheral neuropathy is associated with an ABCB1 single nucleotide polymorphism and older age in Japanese2017
Author(s)
Tanabe Y, Shimizu C, Hamada A, Hashimoto K, Ikeda K, Nishizawa D, Hasegawa J, Shimomura A, Ozaki Y, Tamura N, Yamamoto H, Yunokawa M, Yonemori K, Takano T, Kawabata H, Tamura K, Fujiwara Y
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Journal Title
Cancer Chemother Pharmacol
Volume: 79(6)
Issue: 6
Pages: 1179-1186
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] ゲノムワイド関連解析 (GWAS) による腹腔鏡補助下大腸切除術後フェンタニル必要量に影響する遺伝子多型の同定2017
Author(s)
西澤大輔, 三枝勉, 辻田美紀, 天野功二郎, 田代浄, 石井利昌, 山口茂樹, 笠井慎也, 長谷川準子, 池田和隆, 北村晶, 林田眞和
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Journal Title
日本神経精神薬理学雑誌
Volume: 37(2)
Pages: 53-54
Related Report
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[Presentation] ゲノムワイド関連解析(GWAS)による慢性痛及び帯状疱疹後神経痛感受性遺伝子の同定2019
Author(s)
西澤大輔, 有田英子, 花岡一雄, 矢島直, 井関雅子, 加藤実, 小川節郎, 平沼彩子, 笠井慎也, 長谷川準子, 江畑裕子, 中山京子, 林田眞和, 池田和隆
Organizer
日本人類遺伝学会第64回大会
Related Report
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[Presentation] Genome-wide association study identifies genetic polymorphisms and genes possibly associated with chronic pain and postherpetic neuralgia2019
Author(s)
Nishizawa D, Arita H, Hanaoka K, Yajima C, Iseki M, Kato J, Ogawa S, Hiranuma A, Kasai S, Hasegawa J, Ebata Y, Nakayama K, Hayashida M, Ikeda K
Organizer
The American Society of Human Genetics 69th Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Association between the rs11726196 Single-Nucleotide Polymorphism within the Transient Receptor Subfamily C Member 3 (TRPC3) Gene and Chronic Pain2019
Author(s)
Aoki Y, Nishizawa D, Yoshida K, Arita H, Hanaoka K, Yajima C, Iseki M, Kato J, Ogawa S, Hiranuma A, Hasegawa J, Kasai S, Takahashi K, Koukita Y, Ichinohe T, Hayashida M, Fukuda K, Ikeda K
Organizer
6th Congress of Asian College of Neuropsychopharmacology (AsCNP2019)
Related Report
Int'l Joint Research
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[Presentation] Genome-wide association studies on chronic pain and effects of drugs for the treatment of pain2019
Author(s)
Nishizawa D, Arita H, Hanaoka K, Yajima C, Iseki M, Kato J, Ogawa S, Hiranuma A, Kasai S, Hasegawa J, Ebata Y, Nakayama K, Hayashida M, Ikeda K
Organizer
6th Congress of Asian College of Neuropsychopharmacology (AsCNP2019)
Related Report
Int'l Joint Research
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[Presentation] Associations between genetic polymorphisms on chromosome 14q32 and effects of opioid analgesics and chronic pain2019
Author(s)
Kosaki Y, Nishizawa D, Arita H, Hanaoka K, Yajima C, Iseki M, Kato J, Ogawa S, Hiranuma A, Kasai S, Hasegawa J, Nakayama K, Ebata Y, Koukita Y, Ichinohe T, Hayashida M, Fukuda K, Ikeda K
Organizer
6th Congress of Asian College of Neuropsychopharmacology (AsCNP2019)
Related Report
Int'l Joint Research
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[Presentation] ゲノムワイド関連解析(GWAS)による冷水誘発疼痛試験におけるフェンタニルの鎮痛効果と関連する遺伝子多型の同定2018
Author(s)
西澤大輔, 髙橋香央里, 吉田香織, 笠井慎也, 長谷川準子, 中山京子, 江畑裕子, 高北義彦, 福田謙一, 一戸達也, 池田和隆
Organizer
第28回日本臨床精神神経薬理学会・第48回日本神経精神薬理学会 合同年会
Related Report
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[Presentation] Genome-wide association study identifies gene polymorphisms associated with the analgesic effect of fentanyl in the preoperative cold pressor-induced pain test2018
Author(s)
Nishizawa D, Takahashi K, Yoshida K, Kasai S, Hasegawa J, Nakayama K, Ebata Y, Koukita Y, Fukuda K, Ichinohe T, Ikeda K
Organizer
The American Society of Human Genetics 68th Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Genome-wide association study identifies genetic polymorphisms associated with the analgesic effect of fentanyl in the preoperative cold pressor-induced pain test2018
Author(s)
Nishizawa D, Takahashi K, Yoshida K, Kasai S, Hasegawa J, Nakayama K, Ebata Y, Koukita Y, Fukuda K, Ichinohe T, Ikeda K
Organizer
31st CINP World Congress
Related Report
Int'l Joint Research
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[Presentation] The orexin (hypocretin) receptor 2 gene polymorphism Val308Ile associated with nicotine dependence2018
Author(s)
Nishizawa D, Kasai S, Hasegawa J, Sato N, Yamada H, Tanioka F, Nagashima M, Ujike H, Hashimoto R, Arai T, Mori S, Sawabe M, Naka-Mieno M, Yamada Y, Yamada M, Sato N, Muramatsu M, Tanaka M, Hayashida M, Sugimura H, Ikeda K
Organizer
2018 NIDA International Forum
Related Report
Int'l Joint Research
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[Presentation] Associations between the orexin (hypocretin) receptor 2 gene polymorphism Val308Ile and nicotine dependence found in genome-wide and subsequent association studies2018
Author(s)
Nishizawa D, Kasai S, Hasegawa J, Sato N, Yamada H, Tanioka F, Nagashima M, Ujike H, Hashimoto R, Arai T, Mori S, Sawabe M, Naka-Mieno M, Yamada Y, Yamada M, Sato N, Muramatsu M, Tanaka M, Hayashida M, Sugimura H, Ikeda K
Organizer
CPDD 80th Annual Scientific Meeting
Related Report
Int'l Joint Research
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[Presentation] ゲノムワイド関連解析(GWAS)による慢性疼痛感受性遺伝子多型の同定2017
Author(s)
西澤大輔, 有田英子, 花岡一雄, 矢島直, 井関雅子, 加藤実, 小川節郎, 平沼彩子, 笠井慎也, 長谷川準子, 林田眞和, 池田和隆
Organizer
日本人類遺伝学会第62回大会
Related Report
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[Presentation] Genome-wide association study identifies candidate loci associated with intraoperative remifentanil requirements during laparoscopic-assisted colectomy2017
Author(s)
Nishizawa D, Mieda T, Tsujita M, Nakagawa H, Yamaguchi S, Kasai S, Hasegawa J, Fukuda K, Kitamura A, Hayashida M, Ikeda K
Organizer
The American Society of Human Genetics 67th Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Associations between polymorphisms close to the cAMP responsive element binding protein 1 (CREB1) gene and the activating transcription factor 2 (ATF2) gene and fentanyl sensitivity2017
Author(s)
Aoki Y, Nishizawa D, Yoshida K, Hasegawa J, Kasai S, Takahashi K, Koukita Y, Ichinohe T, Hayashida M, Fukuda K, Ikeda K
Organizer
5th Congress of Asian College of Neuropsychopharmacology (AsCNP 2017)
Related Report
Int'l Joint Research
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