Post-GWAS study for identification of druggable target of AF
Project/Area Number |
26293052
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
General pharmacology
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
笹野 哲郎 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (00466898)
井原 健介 東京医科歯科大学, 難治疾患研究所, 教授 (50770210)
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Project Period (FY) |
2014-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
|
Keywords | 心房細動 / ゲノムワイド関連解析 / 1塩基多型 / GWAS / 酸化ストレス / 交感神経 / 不整脈 / 遺伝子多型 / 薬理学 / 循環器・高血圧 / マイクロRNA |
Outline of Final Research Achievements |
Genome-wide association study (GWAS) has been introduced as a tool to examine genetic risk of common diseases and to deploy personalized medicine. As a by-product of GWAS, it is also expected to identify novel pathogenic pathways and thus novel druggable targets. Atrial fibrillation (AF) is the most frequent arrhythmia and associated cerebral infarction (cardiogenic embolism) is the main cause of disability. We performed 3 GWASs for AF, and found 14 AF-sensitive single nucleotide polymorphisms (SNPs) in Japanese population. Against these 14 SNPs, we performed functional assay to identify novel druggable targets. There are SNPs associated with oxidative stress, myolysis, or differentiation of sympathetic nerve. These findings provide novel pathogenic pathways of AF, and are suggested to a potential targets of AF drugs.
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Report
(5 results)
Research Products
(69 results)
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[Journal Article] Combined analysis of human and experimental murine samples identified novel circulating microRNAs as biomarker for atrial fibrillation2018
Author(s)
Natusme Y, Oaku K, Takahashi K, Nakamura W, Oono A, Hamada S, Yamazoe M, Ihara K, Sasaki T, Goya M, Hirao K, Furukawa T, Sasano T
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Journal Title
Circ. J.
Volume: 82
Pages: 965-973
DOI
Related Report
Peer Reviewed
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[Journal Article] Flecainide ameliorates arrhythmogenicity through NCX flux in Andersen-Tawil syndrome-iPS cell-derived cardiomyocytes2017
Author(s)
Kuroda Y, Yuasa S, Watanabe Y, Ito S, Egashira T, Seki T, Hattori T, Ohno S, Kodaira M, Suzuki T, Hashimoto H, Okata S, Tanaka A, Aizawa Y, Murata M, Aiba T, Makita N, Furukawa T, Shimizu W, Kodama I, Ogawa S, Kokubun N, Horigome H, Horie M, Kamiya K, Fukuda K
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Journal Title
Biochem. Biophys. Rep.
Volume: 9
Pages: 245-256
DOI
Related Report
Peer Reviewed
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[Journal Article] Association of ZFHX3 gene variation with atrial fibrillation, cerebral infarction, and lung thromboembolism: An autopsy study2017
Author(s)
Zaw KTT, Sato N, Ikeda S, Thu KS, Mieno MN, Arai T, Mori S, Furukawa T, Sasano T, Sawabe M, Tanaka M, Muramatsu M
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Journal Title
J. Cardiol.
Volume: 70
Pages: 180-184
DOI
Related Report
Peer Reviewed
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[Journal Article] Identification of six new genetic loci associated with atrial fibrillation in the Japanese population2017
Author(s)
Low SK, Takahashi A, Ebana Y, Ozaki K, Christophersen IE, Ellinor PT; AFGen Consortium., Ogishima S, Yamamoto M, Satoh M, Sasaki M, Yamaji T, Iwasaki M, Tsugane S, Tanaka K, Naito M, Wakai K, Tanaka H, Furukawa T, Kubo M, Ito K, Kamatani Y, Tanaka T
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Journal Title
Nat. Genet.
Volume: 49
Pages: 953-958
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Chromosome 4q25 variants and recurrence after second-generation cryoballoon ablation in patients with paroxysmal atrial fibrillation2017
Author(s)
Miyazaki S, Ebana Y, Liu L, Nakamura H, Hachiya H, Taniguchi H, Takagi T, Kajiyama T, Watanabe T, Igarashi M, Kusa S, Niida T, Iesaka Y, Furukawa T
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Journal Title
Int. J. Cardiol.
Volume: 244
Pages: 151-157
DOI
Related Report
Peer Reviewed
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[Journal Article] Intravital imaging of Ca2+ signals in lymphocytes of Ca2+ biosensor transgenic mice: indication of autoimmune diseases before the pathological onset2016
Author(s)
Yoshioka S, Usami T, Kikuta J, Ishii M, Sasano T, Sugiyama K, Furukawa T, Nakasho E, Takayanagi H, Tedder T, Karasuyama H, Kiyawami A, Adachi T
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Journal Title
Science Reports
Volume: 1
Pages: 18738
DOI
Related Report
Peer Reviewed
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[Journal Article] Genetic defects in a His-Purkinje system transcription factor, IRX3, cause lethal cardiac arrhythmias2016
Author(s)
Koizumi A, Sasano T, Kimura W, Miyamoto Y, Aiba T, Ishikawa T, Nogami A, Fukamizu S, Sakurada H, Takahashi Y, Nakamura H, Ishikura T, Koseki H, Arimura T, Kimura A, Hirao K, Isobe M, Shimizu W, Miura N, Furukawa T
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Journal Title
European Heart Journal
Volume: 37
Pages: 1469-1475
DOI
Related Report
Peer Reviewed
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[Journal Article] Novel dielectric coagulation identifies hypercoagulability in patients with a high CHADS2 score without atrial fibrillation2016
Author(s)
Hasegawa Y, Hamada S, Nishimura T, Sasaki T, Ebana Y, Kawabata M, Goya M, Isobe M, Koyama T, Furukawa T, Hirao K, Sasano T
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Journal Title
PLoS One
Volume: 11
Pages: e0156557
DOI
Related Report
Peer Reviewed
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[Journal Article] Embryonic type Na+ channel beta-subunit, SCN3B masks the disease phenotype of Brugada syndrome2016
Author(s)
Okata S, Yuasa S, Suzuki T, Ito S, Makita N, Yoshida T, Li M, Kurokawa J, Seki T, Egashira T, Aizawa Y, Kodaira M, Motoda C, Yozu G, Shimojima M, Hayashiji N, Hashimoto H, Kuroda Y, Tanaka A, Murata M, Aiba T, Shimizu W, Horie M, Kamiya K, Furukawa T, Fukuda K
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Journal Title
Scientific Reports
Volume: 6
Pages: 34198
DOI
Related Report
Peer Reviewed
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[Journal Article] Fibroblast growth factors and vascular endothelial growth factor promote cardiac reprogramming under defined conditions2015
Author(s)
Yamakawa H, Muraoka N, Miyamoto K, Sadahiro T, Isomi M, Haginiwa S, Kojima H, Umei T, Akiyama M, Kuishi Y, Kurokawa J, Furukawa T, Fukuda K, Ieda M
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Journal Title
Stem Cell Reports
Volume: 5
Pages: 1128-1142
DOI
Related Report
Peer Reviewed
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[Journal Article] Enhancement of spontaneous activity by HCN4 overexpression in mouse embryonic stem cell-derived cardiomyocytes – A possible biological pacemaker2015
Author(s)
Saito Y, Nakamura K, Yoshida M, Sugiyama H, Ohe T, Kurokawa J, Furukawa T, Takano M, Nagase S, Morita H, Kusano KF, Ito H
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Journal Title
PLoS ONE
Volume: 10
Pages: e0318193
DOI
Related Report
Peer Reviewed
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[Journal Article] Intravital imaging of Ca2+ signals in lymphocytes of Ca2+ biosensor transgenic mice: indication of autoimmune diseases before the pathological onset2015
Author(s)
Yoshioka S, Usami T, Kikuta J, Ishii M, Sasano T, Sugiyama K, Furukawa T, Nakasho E, Takayanagi H, Tedder T, Karasuyama H, Kiyawami A, Adachi T
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Journal Title
Science Report
Volume: 6
Pages: 18738
DOI
Related Report
Peer Reviewed
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[Journal Article] Integrating genetic, transcriptional, and functional analyses to identify five novel genes for atrial fibrillation2014
Author(s)
Sinner MF, Tucker N, Lunetta K, Ozaki K, Smith G, Trompet S, Bis J, Lin H, Chung M, Nielsen JB, Lubitz S, Krijthe B, Magnani J, Ye J, Gollob M, Tsunoda T, Müller-Nurasyid M, Lichtner P, Peters A, Dolmatova E, Kubo M, Smith J, Psaty B, Smith N, Jukema JW, Chasman D, Ebana Y, Furukawa T, et al. (他27名)
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Journal Title
Circulation
Volume: 130
Pages: 1225-1235
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Effect of SNP 9q22 (rs6479562) on the progression from patoxysmal atrial fibrillation to persistent atrial fibrillation2017
Author(s)
Sekigawa M, Satoh A, Nitta J, Sato Y, Honda Y, Kuroda S, Kanoh M, Suzuki M, Inaba O, Muramatsu K, Yamato T, Matsumura Y, Asakawa K, Ebana Y, Furukawa T, Hirao K, Isobe M
Organizer
The 78th Annual Scientific Meeting of the Japanese Circulation Society
Related Report
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[Presentation] Impact of SNP on IL6R (rs7514452) for age at onset of atrial fibrillation2017
Author(s)
Sato Y, Satoh A, Nitta J, Honda Y, Kuroda S, Skigawa M, Kanoh M, Suzuki M, Inaba O, Muramatsu K, Yamato T, Matsumura Y, Asakawa K, Eban Y, Furukawa T, Hirao K, Isobe M
Organizer
The 78th Annual Scientific Meeting of the Japanese Circulation Society
Related Report
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[Presentation] Disease modeling using iPS cells2017
Author(s)
Furukawa T, Okata S, Yuasa S, Suzuki T, Makita N, Kurokawa J, Egashira T, Yamakawa H, Seki T, Aizawa T, Hashimoto H, Kuroda Y, Tanaka A, Yae K, Kurata M, Aiba T, Shimizu W, Horie M, Kodama I, Ogawa S, Fukuda K
Organizer
The 78th Annual Scientific Meeting of the Japanese Circulation Society
Related Report
Invited
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[Presentation] Individual evaluation of whole blood coagulability and factor Xa activity by novel dielectric blood coagulometry2016
Author(s)
Sasano T, Hamada S, Hasegawa Y, Nishimura T, Yoshitake T, Shiohira S, Sasaki T, Kawabata M, Goya M, Isobe M, Furukawa T, Hirao K
Organizer
第63回日本不整脈心電学会
Place of Presentation
札幌コンベンションセンター、札幌市、北海道
Year and Date
2016-07-17
Related Report
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[Presentation] Gene-Guided Therapy in A2016
Author(s)
Furukawa T, Liu L, Ebana Y, Nitta J, Takahashi Y, Miyazaki M, Isobe M, Tanaka T
Organizer
Heart Rhythm Society's 37th Annual Scientific Sessions
Place of Presentation
San Francisco, USA
Year and Date
2016-05-06
Related Report
Int'l Joint Research / Invited
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[Presentation] The occurrence of ectopy from pulmonary veins in atrial fibrillation in middle-aged women2016
Author(s)
Hayashi Y, Nitta J, Iwasaki T, Lee K, Watanabe K, Hirao T, Kato N, Inamura Y, Suzuki M, Negi K, Satoh A, Yamato T, Matsumurea Y, Asakawa K, Ebana Y, Furukawa T, Gohya M, Hirao K, Isobe M
Organizer
The 80th Annual Scientific Meeting of the Japanese Circulation Society
Place of Presentation
仙台国際センター(宮城県/仙台市)
Year and Date
2016-03-18 – 2016-03-20
Related Report
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[Presentation] The genotype of SNPs related whether ectopy is from pulmonary vein or others in atrial fibrillation2016
Author(s)
Hayashi Y, Nitta J, Iwasaki T, Lee K, Watanabe K, Hirao T, Kato N, Inamura Y, Suzuki M, Negi K, Satoh A, Yamato T, Matsumurea Y, Asakawa K, Ebana Y, Furukawa T, Gohya M, Hirao K, Isobe M
Organizer
The 80th Annual Scientific Meeting of the Japanese Circulation Society
Place of Presentation
仙台国際センター(宮城県/仙台市)
Year and Date
2016-03-18 – 2016-03-20
Related Report
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[Presentation] 心房細動とアンチエイジング2015
Author(s)
古川哲史
Organizer
第15回日本抗加齢医学会総会
Place of Presentation
福岡国際会議場(福岡県/福岡市)
Year and Date
2015-05-30 – 2015-05-31
Related Report
Invited
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