2019 Fiscal Year Final Research Report
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 |
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| Section | 一般 |
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| Research Field |
Applied pharmacology
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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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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| 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 |
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| 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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| Free Research Field |
人類遺伝学
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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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