What exists between schizophrenia and bipolar disorder ~genomic analysis by whole-genome resequence~

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K10196
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Osaka Medical College
• Principal Investigator: Kanazawa Tetsufumi 大阪医科大学, 医学部, 教授 (20534100)
• Co-Investigator(Kenkyū-buntansha): 橋口 康之 大阪医科大学, 医学部, 講師 (70436517)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 非定型精神病 / 次世代シーケンサー / 全ゲノムシーケンス / 多発家系 / 統合失調症 / 双極性障害 / 遺伝子研究 / DCC

Outline of Final Research Achievements

Atypical psychosis (similar to acute and transient psychotic disorder) is highly heritable, but the causal genes remain unidentified. We conducted whole-genome sequencing on multiplex Japanese families with atypical psychosis. In addition to the next-generation analysis, HLA typing has been conveyed to check the similarity with autoimmune disease, such as systemic lupus erythematosus (SLE). Shared causal polymorphisms in the Deleted in Colorectal Carcinoma, Netrin 1 receptor (DCC) gene were found in one multiplex family with three patients, and One Cut Homeobox 2 (ONECUT2) genes were found to be shared in seven patients. Next-generation sequencing analysis of the MHC region (previously suggested to be a hot region in atypical psychosis) using HLA typing (HLA-DRB1) revealed a common vulnerability with SLE (systemic lupus erythematosus) among five patients. Focusing on a specific clinical phenotype is key for elucidating the genetic factors that underlie the complex traits of psychosis.

Free Research Field

精神科遺伝学

Academic Significance and Societal Importance of the Research Achievements

これまで明らかにされていなかった非定型精神病、すなわち急性に精神病症状を呈し、周期的に再発を繰り返す患者の遺伝学的特徴を世界で初めて捕捉することができた。これは詳細な遺伝子調査が可能な次世代シーケンサーによってでしか成し遂げられない成果で、さらに自己免疫疾患であるSLEとの遺伝的な近しさを明らかにしえたことで、これまで謎であった両者の症状における近似性の秘密を遺伝学を用いて白日の下に晒したといえる。