Identification of rare genetic variants associated with bipolar disorder and comprehensive analysis to elucidate its pathophysiology
Project/Area Number |
25253072
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Psychiatric science
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Research Institution | Nagoya University |
Principal Investigator |
OZAKI Norio 名古屋大学, 医学(系)研究科(研究院), 教授 (40281480)
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Co-Investigator(Renkei-kenkyūsha) |
IRITANI Syuji 名古屋大学, 大学院医学系研究科, 寄附講座教授 (60191904)
IIDAKA Tetsuya 名古屋大学, 大学院医学系研究科, 准教授 (70324366)
ALEKSIC Branko 名古屋大学, 大学院医学系研究科(国際), 特任准教授 (60547511)
KUNIMOTO Shohko 名古屋大学, 大学院医学系研究科, 特任助教 (30350135)
KANBA Shigenobu (NODA Yukihiro / OKANO Hideyuki / IWATA Nakao) 九州大学, 医学部, 教授 (60312112)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥45,500,000 (Direct Cost: ¥35,000,000、Indirect Cost: ¥10,500,000)
Fiscal Year 2015: ¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2014: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Fiscal Year 2013: ¥23,400,000 (Direct Cost: ¥18,000,000、Indirect Cost: ¥5,400,000)
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Keywords | 双極性障害 / ゲノムコピー数変異 / ゲノムコピー数多型 / CNV |
Outline of Final Research Achievements |
We performed a high-resolution genome-wide copy number variation (CNV) analysis on Japanese patients with bipolar disorder (BP). We identified clinically significant CNVs in around 6% of BP patients. Among others, PCDH15 (protocadherin 15) was identified as a promising candidate gene because exonic deletions were observed in three patients. From two BP patients with PCDH15 deletions, we established induced pluripotent stem (iPS) cell lines. We applied genome-modifying technology of CRISPR/Cas9 method and generated the Pcdh15-deficient mice, carrying the NHEJ mutant allele.
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] The Disrupted-in-Schizophrenia-1 Ser704Cys polymorphism and brain neurodevelopmental markers in schizophrenia and healthy subjects.2015
Author(s)
Takahashi T, Nakamura M, Nakamura Y, Aleksic B, Kido M, Sasabayashi D, Takayanagi Y, Furuichi A, Nishikawa Y, Noguchi K, Ozaki N, Suzuki M
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Journal Title
Prog Neuropsychopharmacol Biol Psychiatry
Volume: 56
Pages: 11-17
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of Rare, Single-Nucleotide Mutations in NDE1 and Their Contributions to Schizophrenia Susceptibility.2015
Author(s)
Kimura H, Tsuboi D, Wang C, Kushima I, Koide T, Ikeda M, Iwayama Y, Toyota T, Yamamoto N, Kunimoto S, Nakamura Y, Yoshimi A, Banno M, Xing J, Takasaki Y, Yoshida M, Aleksic B, Uno Y, Okada T, Iidaka T, Inada T, Suzuki M, Ujike H, Kunugi H, Kato T, Yoshikawa T, Iwata N, Kaibuchi K
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Journal Title
Schizophrenia Bulltein
Volume: 41
Issue: 3
Pages: 744-753
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Association study of BCL9 gene polymorphism rs583583 with schizophrenia and negative symptoms in Japanese population.2015
Author(s)
Kimura H, Tanaka S, Kushima I, Koide T, Banno M, Kikuchi T, Nakamura Y, Shiino T, Yoshimi A, Oya-Ito T, Xing J, Wang C, Takasaki Y, Aleksic B, Okada T, Ikeda M, Inada T, Iidaka T, Iwata N, Ozaki N.
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Journal Title
Scientific reports
Volume: 5
Issue: 1
Pages: 15705-15705
DOI
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Blonanserin ameliorates phencyclidine-induced visual-recognition memory deficits: the complex mechanism of blonanserin action involving D3-5-HT2A and D1-NMDA receptors in the mPFC2015
Author(s)
Hida H, Mouri A, Mori K, Matsumoto Y, Seki T, Taniguchi M, Yamada K, Iwamoto K, Ozaki N, Nabeshima T, Noda Y
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Journal Title
Neuropsychopharmacology
Volume: 40
Issue: 3
Pages: 601-613
DOI
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] No support for replication of the genetic variants identified by a recent mega-analysis of the treatment response to antidepressants2015
Author(s)
Hatano M, Ikeda M, Kondo K, Saito T, Shimasaki A, Esaki K, Umene-Nakano W, Yoshimura R, Nakamura J, Ozaki N, Iwata N
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Journal Title
J Hum Genet
Volume: in press
Issue: 6
Pages: 343-344
DOI
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Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Replication and cross-phenotype study based upon schizophrenia GWASs data in the Japanese population: support for association of MHC region with psychosis.2014
Author(s)
Saito T, Kondo K, Iwayama Y, Shimasaki A, Aleksic B, Yamada K, Toyota T, Hattori E, Esaki K, Ujike H, Inada T, Kunugi H, Kato T, Yoshikawa T, Ozaki N, Ikeda M, Iwata N.
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Journal Title
Am J Med Genet B Neuropsychiatr Genet
Volume: 165
Issue: 5
Pages: 421-427
DOI
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Peer Reviewed / Open Access
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[Journal Article] Genetic association study between the detected risk variants based upon type II diabetes GWAS and psychotic disorders in the Japanese population.2014
Author(s)
Kajio Y, Kondo K, Saito T, Iwayama Y, Aleksic B, Yamada K, Toyota T, Hattori E, Ujike H, Inada T, Kunugi H, Kato T, Yoshikawa T, Ozaki N, Ikeda M, Iwata N.
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Journal Title
J Hum Genet
Volume: 59
Issue: 1
Pages: 54-56
DOI
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Peer Reviewed
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[Journal Article] Genome-wide association study identifies a potent locus associated with human opioid sensitivity.2014
Author(s)
Nishizawa D, Fukuda K, Kasai S, Hasegawa J, Aoki Y, Nishi A, Saita N, Koukita Y, Nagashima M, Katoh R, Satoh Y, Tagami M, Higuchi S, Ujike H, Ozaki N, Inada T, Iwata N, Sora I, Iyo M, Kondo N, Won MJ, Naruse N, Uehara-Aoyama K, Itokawa M, Koga M, Arinami T, Kaneko Y, Hayashida M, Ikeda K.
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Journal Title
Mol Psychiatry
Volume: 19(1)
Issue: 1
Pages: 55-62
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Peer Reviewed
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[Journal Article] Plasma dehydroepiandrosterone sulfate levels in patients with major depressive disorder correlate with remission during treatment with antidepressants2014
Author(s)
Tokiko Morita, Koji Senzaki, Ryoko Ishihara, Kazunori Umeda, Nakao Iwata, Taku Nagai, Hirotake Hida, Toshitaka Nabeshima, Kazunori Yukawa, Norio Ozaki, Yukihiro Noda
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Journal Title
Hum. Psychopharmacol.: Clin. Exp.
Volume: 29
Issue: 3
Pages: 280-286
DOI
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Peer Reviewed / Open Access
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[Journal Article] Factor structure of the Japanese version of the edinburgh postnatal depression scale in the postpartum period.2014
Author(s)
Kubota C, Okada T, Aleksic B, Nakamura Y, Kunimoto S, Morikawa M, Shiino T, Tamaji A, Ohoka H, Banno N, Morita T, Murase S, Goto S, Kanai A, Masuda T, Ando M, Ozaki N
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Journal Title
PLoS One
Volume: 9
Issue: 8
Pages: e103941-e103941
DOI
Related Report
Peer Reviewed
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[Journal Article] A Population-Specific Uncommon Variant in GRIN3A Associated with Schizophrenia.2013
Author(s)
Takata A, Iwayama Y, Fukuo Y, Ikeda M, Okochi T, Maekawa M, Toyota T, YamadaK, Hattori E, Ohnishi T, Toyoshima M, Ujike H, Inada T, Kunugi H, Ozaki N, Nanko S, Nakamura K, Mori N, Kanba S, Iwata N, Kato T, Yoshikawa T.
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Journal Title
Biol Psychiatry.
Volume: 73(6)
Issue: 6
Pages: 532-9
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Peer Reviewed
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[Journal Article] Common variants in bcl9 gene and schizophrenia in a japanese population: Association study, meta-analysis and cognitive function analysis.2013
Author(s)
Shiino T, Koide T, Kushima I, Ikeda M, Kunimoto S, Nakamura Y, Yoshimi A, Aleksic B, Banno M, Kikuchi T, Kohmura K, Adachi Y, Kawano N, Okada T, Inada T, Ujike H, Iidaka T, Suzuki M, Iwata N, Ozaki N
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Journal Title
J Med Biochem
Volume: 32 (4)
Pages: 351-357
Related Report
Peer Reviewed
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[Journal Article] Functional analysis of deep intronic SNP rs13438494 in intron 24 of PCLO gene2013
Author(s)
Seo S, Takayama K, Uno K, Ohi K, Hashimoto R, Nishizawa D, Ikeda K, Ozaki N, Nabeshima T, Miyamoto Y, Nitta A
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Journal Title
PLoS ONE
Volume: 8(10)
Issue: 10
Pages: e76960-e76960
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Peer Reviewed
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[Journal Article] Genetic variants on 3q21 and in the Sp8 transcription factor gene (SP8) as susceptibility loci for psychotic disorders : a genetic association study2013
Author(s)
Kondo K, Ikeda M, Kajio Y, Saito T, Iwayama Y, Aleksic B, Yamada K, Toyota T, Hattori E, Ujike H, Inada T, Kunugi H, Kato T, Yoshikawa T, Ozaki N, Iwata N
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Journal Title
PLoS One
Volume: 8(8)
Issue: 8
Pages: e70964-e70964
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Related Report
Peer Reviewed
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[Journal Article] Lack of association of EGR2 variants with bipolar disorder in Japanese population2013
Author(s)
Balan S, Yamada K, Iwayama Y, Toyota T, Ohnishi T, Maekawa M, Toyoshima M, Iwata Y, Suzuki K, Kikuchi M, Ujike H, Inada T, Kunugi H, Ozaki N, Iwata N, Nanko S, Kato T, Yoshikawa T
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Journal Title
Gene
Volume: 526(2)
Issue: 2
Pages: 246-250
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Peer Reviewed
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[Journal Article] Definition and refinement of the 7q36.3 duplication region associated with schizophrenia2013
Author(s)
Aleksic B, Kushima I, Ohye T, Ikeda M, Kunimoto S, Nakamura Y, Yoshimi A, Koide T, Iritani S, Kurahashi H, Iwata N, Ozaki N
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Journal Title
Sci Rep
Volume: 3
Issue: 1
Pages: 2587-2587
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Peer Reviewed
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[Journal Article] Analysis of the VAV3 as candidate gene for schizophrenia : evidences from voxel based morphometry and mutation screening.2012
Author(s)
Aleksic B, Kushima I, Hashimoto R, Ohi K, Ikeda M, Yoshimi A, Nakamura Y, Ito Y, Okochi T, Fukuo Y, Yasuda Y, Fukumoto M, Yamamori H, Ujike H, Suzuki M, Inada T, Takeda M, Kaibuchi K, Iwata N, Ozaki N
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Journal Title
Schizophrenia Bulletin
Volume: 39
Issue: 3
Pages: 39-39
DOI
Related Report
Peer Reviewed