Detecting genetic component of schizophrenia

• Project/Area Number: 25293253
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Fujita Health University
• Principal Investigator: Iwata Nakao 藤田保健衛生大学, 医学部, 教授 (60312112)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥19,500,000 (Direct Cost: ¥15,000,000、Indirect Cost: ¥4,500,000); Fiscal Year 2015: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
• Keywords: 遺伝学 / 精神科遺伝学

Outline of Final Research Achievements

A number of genome-wide association studies (GWASs) for schizophrenia have conducted, and now detected multiple susceptibility genes. However, as such locus cannot fully explain the heritability (i.e. missing heritability), rare variants may be the key factor to detect the whole range of the schizophrenia risk. In this study, we conducted a GWAS (for the common variants: SNP) and a target resequencing (for previously implicated loci) in the Japanese population, to detect the susceptibility genes for schizophrenia.
Approximately 5,000 subjects were genotyped, however, we could not find any significant association in SNP nor SNVs with schizophrenia.
Specifically, to examine the existence of the genetic risk within our samples, we conducted a polygenic component analysis: we did find significant enrichment of the risk alleles in our cases, implying accumulative genetic risk exists. Further sample size will be required to identify individual susceptibility SNP for schizophrenia.

Research Products

• [Int'l Joint Research] Psychiatric GWAS Consortium(米国)
• [Journal Article] Pharmacogenomic Study of Clozapine-Induced Agranulocytosis/Granulocytopenia in a Japanese Population (2016)
  • Author(s): Saito T, Ikeda M, Mushiroda T, Ozeki T, Kondo K, Shimasaki A, Kawase K, Hashimoto S, Yamamori H, Yasuda Y, Fujimoto M et al
  • Journal Title: Biol Psychiatry Volume: in press Issue: 8 Pages: 636-642
  • DOI: 10.1016/j.biopsych.2015.12.006
  • NAID: 120007129309
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide environment interaction between depressive state and stressful life events. (2016)
  • Author(s): Ikeda M, Shimasaki A, Takahashi A, Kondo K, Saito T, Kawase K, Esaki K, Otsuka Y, Mano K, Kubo M, Iwata N.
  • Journal Title: J Clin Psychiatry Volume: 77(1) Issue: 01 Pages: e29-e30
  • DOI: 10.4088/jcp.15l10127
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Genetic overlap between antipsychotic response and susceptibility to schizophrenia (2015)
  • Author(s): Ikeda M, Yoshimura R, Hashimoto R, Kondo K, Saito T, Shimasaki A, Ohi K, Tochigi M, Kawamura Y, Nishida N, Miyagawa T, Sasaki T, Tokunaga K, Kasai K, Takeda M, Nakamura J, Ozaki N, Iwata N.
  • Journal Title: Journal of Clinical Psychopharmacology Volume: 35(1) Issue: 1 Pages: 85-88
  • DOI: 10.1097/jcp.0000000000000268
  • Peer Reviewed / Open Access
• [Journal Article] No support for replication of the genetic variants identified by a recent mega-analysis of the treatment response to antidepressants (2015)
  • 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
  • Journal Title: J Hum Genet Volume: in press Issue: 6 Pages: 343-344
  • DOI: 10.1038/jhg.2015.21
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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.
  • Journal Title: Am J Med Genet B Neuropsychiatr Genet Volume: 165 Issue: 5 Pages: 421-427
  • DOI: 10.1002/ajmg.b.32246
  • Peer Reviewed / Open Access
• [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.
  • Journal Title: J Hum Genet Volume: 59 Issue: 1 Pages: 54-56
  • DOI: 10.1038/jhg.2013.116
  • Peer Reviewed
• [Journal Article] Genome-wide association study implicates NDST3 in schizophrenia and bipolar disorder. Nat Commun (2013)
  • Author(s): Lencz T, Guha S, Liu C, Rosenfeld J, Mukherjee S, Derosse P, John M, Cheng L, Zhang C, Badner JA, Ikeda M, Iwata N, Cichon S, Rietschel M, Nothen MM, Cheng AT, Hodgkinson C, Yuan Q, Kane JM, Lee AT, Pisante A, Gregersen PK, Pe'er I, Malhotra AK, Goldman D and Darvasi A
  • Journal Title: Nat Commun Volume: 4) Issue: 5 Pages: 2739-2739
  • DOI: 10.1016/j.biopsych.2013.05.040
  • Peer Reviewed
• [Journal Article] Genetic variants on 3q21 and in the Sp8 transcription factor gene (SP8) as susceptibility loci for psychotic disorders : a genetic association study (2013)
  • 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
  • Journal Title: PLoS One Volume: 8(8) Issue: 8 Pages: e70964-e70964
  • DOI: 10.1371/journal.pone.0070964
  • Peer Reviewed
• [Journal Article] Evidence for shared genetic risk between methamphetamine-induced psychosis and schizophrenia (2013)
  • Author(s): 池田 匡志 他
  • Journal Title: Neuropsychopharmacology Volume: 38 Issue: 10 Pages: 1864-1870
  • DOI: 10.1038/npp.2013.94
  • Peer Reviewed