NGS of multiple onset schizophrenia families

• Project/Area Number: 18K07554
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Nagoya University
• Principal Investigator: Aleksic Branko 名古屋大学, 医学系研究科(国際), 特任准教授 (60547511)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2019: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
• Keywords: exome seqencing / exome sequencing / Whole exome sequencing / Genome / Sequencing / Psychiatry / NGS

Outline of Final Research Achievements

In this research we dissected genetic architecture of schizophrenia using families with multiple affected members. Until now most family based exome sequencing used trio based design and research was focused mainly on de novo variants (i.e. variants that are not present in parents but exist in affected children). In the current research besides de novo variants we focused on inherited variants. These are variants that are present in all affected member in one pedigree. In addition we investigated variants that are rare and of high impact (i.e. splice site mutation and/or nonsense variants), which may be family specific but exhibit incomplete penetrance (i.e. present in both affected and non affected members of the same family.

Academic Significance and Societal Importance of the Research Achievements

This research helped to alleviate misconceptions and reduce stigma through an improved understanding of the genetic cause of psychiatric disorders, and eventually offer support to patients and their families.

Research Products

• [Journal Article] Characterization of a schizophrenia patient with a rare RELN deletion by combining genomic and patient-derived cell analyses (2020)
  • Author(s): Arioka Yuko,Hirata Akihiro,Kushima Itaru,Aleksic Branko,Mori Daisuke,Ozaki Norio
  • Journal Title: Schizophrenia Research Volume: 216 Pages: 511-515
  • DOI: 10.1016/j.schres.2019.10.038
  • Peer Reviewed / Open Access
• [Journal Article] Rare single-nucleotide DAB1 variants and their contribution to Schizophrenia and autism spectrum disorder susceptibility (2020)
  • Author(s): Nawa Yoshihiro、Kimura Hiroki、Mori Daisuke、Kato Hidekazu、Toyama Miho、Furuta Sho、Yu Yanjie、Ishizuka Kanako、Kushima Itaru、Aleksic Branko、Arioka Yuko、Morikawa Mako、Okada Takashi、Inada Toshiya、Kaibuchi Kozo、Ikeda Masashi、Iwata Nakao、Suzuki Michio、Okahisa Yuko、Egawa Jun et al
  • Journal Title: Human Genome Variation Volume: 7 Issue: 1 Pages: 37-37
  • DOI: 10.1038/s41439-020-00125-7
  • Peer Reviewed / Open Access
• [Journal Article] Pharmacotherapy of restricted/repetitive behavior in autism spectrum disorder:a systematic review and meta-analysis (2020)
  • Author(s): Yu Yanjie、Chaulagain Ashmita、Pedersen Sindre Andre、Lydersen Stian、Leventhal Bennett L.、Szatmari Peter、Aleksic Branko、Ozaki Norio、Skokauskas Norbert
  • Journal Title: BMC Psychiatry Volume: 20 Issue: 1
  • DOI: 10.1186/s12888-020-2477-9
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Assessment of a glyoxalase I frameshift variant, p.P122fs, in Japanese patients with schizophrenia. (2018)
  • Author(s): Ishizuka K, Kimura H, Kushima I, Inada T, Okahisa Y, Ikeda M, Iwata N, Mori D, Aleksic B, Ozaki N.
  • Journal Title: Psychiatr Genet. Volume: 5 Issue: 5 Pages: 90-93
  • DOI: 10.1097/ypg.0000000000000204
  • Peer Reviewed / Open Access
• [Journal Article] Rare loss of function mutations in N-methyl-d-aspartate glutamate receptors and their contributions to schizophrenia susceptibility (2018)
  • Author(s): Yu Yanjie、Lin Yingni、Takasaki Yuto、Wang Chenyao、Kimura Hiroki、Xing Jingrui、Ishizuka Kanako、Toyama Miho、Kushima Itaru、Mori Daisuke、Arioka Yuko、Uno Yota、Shiino Tomoko、Nakamura Yukako、Okada Takashi、Morikawa Mako、Ikeda Masashi、Iwata Nakao、Okahisa Yuko、Takaki Manabu、Sakamoto Shinji、et al.
  • Journal Title: Translational Psychiatry Volume: 8 Issue: 1 Pages: 12-20
  • DOI: 10.1038/s41398-017-0061-y
  • Peer Reviewed / Open Access / Int'l Joint Research