Association analysis between classical HLA and schizophrenia

• Project/Area Number: 26293266
• 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: Ikeda Masashi 藤田保健衛生大学, 医学部, 准教授 (60424933)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000); Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
• Keywords: 臨床精神分子遺伝学 / 精神科遺伝学 / 遺伝学 / 精神医学 / 統合失調症

Outline of Final Research Achievements

MHC region including HLA is promising candidate region for schizophrenia based on genome-wide association studies (GWASs). In this study, we focused on the classical HLA, and conducted association analysis using relatively large sample size (2500 schizophrenia and 3000 controls in the Japanese population). However, we could not detect significant association between specific HLA allele and schizophrenia.
In summary we speculate that the GWAS signal in the MHC region may not point the classical HLA, but non-HLA genes as risk genes for schizophrenia.

Research Products

• [Journal Article] A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder. (2018)
  • Author(s): Ikeda M, Shimasaki A, Takahashi A,et al.
  • Journal Title: Mol Psychiatry. Volume: in press Pages: 639-647
  • DOI: 10.1038/mp.2016.259
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Transethnic Replication Study to Assess the Association Between Clozapine-Induced Agranulocytosis/Granulocytopenia and Genes at 12p12.2 in a Japanese Population (2017)
  • Author(s): Saito T, Ikeda M, Hashimoto R, Iwata N; Members of the Clozapine Pharmacogenomics Consortium of Japan
  • Journal Title: Biol Psychiatry Volume: in press
  • DOI: 10.1016/j.biopsych.2016.12.009
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Risk factors and clinical characteristics of the depressive state induced by pegylated interferon therapy in patients with hepatitis C virus infection: A prospective study. (2016)
  • Author(s): 3.Kawase K, Kondo K, Saito T, Shimasaki A, Takahashi A, Kamatani Y, Kawabe N, Hashimoto S, Ikeda M, Kubo M, Yoshioka K, Iwata N
  • Journal Title: Psychiatry Clin Neurosci Volume: 70(11) Pages: 489-497
  • DOI: 10.1111/pcn.12424
  • Peer Reviewed / Acknowledgement Compliant
• [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 Pages: 636-42
  • DOI: 10.1016/j.biopsych.2015.12.006
  • NAID: 120007129309
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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)
  • DOI: 10.4088/jcp.15l10127
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Common genetic variants influence human subcortical brain structures (2015)
  • Author(s): Hibar P ,,,, Ikeda M,,,,et al
  • Journal Title: Nature Volume: 520 Pages: 224-229
  • DOI: 10.1038/nature14101
  • Peer Reviewed
• [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 Pages: 343-344
  • DOI: 10.1038/jhg.2015.21
  • 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) Pages: 85-8
  • DOI: 10.1097/jcp.0000000000000268
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A genetic variant in 12q13, a possible risk factor for bipolar disorder, is associated with depressive state, accounting for stressful life events (2014)
  • Author(s): Shimasaki A, Kondo K, Saito T, Esaki K, Otsuka Y, Mano K, Ikeda M, Iwata N
  • Journal Title: PLoS One Volume: 9
  • DOI: 10.1371/journal.pone.0115135
  • Peer Reviewed / 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: m J Med Genet B Neuropsychiatr Genet Volume: 165 Pages: 421-427
  • DOI: 10.1002/ajmg.b.32246
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 「若手研究者育成プログラム」、シンポジウム (2016)
  • Author(s): 池田匡志
  • Organizer: 日本生物学的精神医学会
  • Place of Presentation: 福岡
  • Invited
• [Presentation] 気分障害の遺伝学的研究;薬理ゲノム学と疾患感受性 (2016)
  • Author(s): 池田匡志
  • Organizer: 日本生物学的精神医学会
  • Place of Presentation: 福岡
  • Invited
• [Presentation] 精神科遺伝子研究：臨床応用への問題点と今後の戦略 ;PGxに焦点を当てて (2015)
  • Author(s): 池田匡志
  • Organizer: 日本臨床精神薬理学会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2015-10-29
• [Presentation] 精神疾患の薬理ゲノム学 (2015)
  • Author(s): 池田匡志
  • Organizer: 日本生物学的精神医学会
  • Place of Presentation: タワーホール船堀
  • Year and Date: 2015-09-26
• [Presentation] 精神疾患のゲノム研究 (2015)
  • Author(s): 池田匡志
  • Organizer: 日本精神神経学会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2015-06-04