Investigation of genome and epigenome factors in elderly patients with mood disorders

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K15486
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52030:Psychiatry-related
• Research Institution: Osaka University (2020-2021); Kumamoto University (2018-2019)
• Principal Investigator: Sugawara Hiroko 大阪大学, 医学系研究科, 招へい教員 (90610692)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 双極性障害 / 高齢者 / SLC6A4 / 5HTTLPR / DNAメチル化

Outline of Final Research Achievements

In this study, I aimed to investigate the genomic and epigenomic factors in elderly patients with mood disorders, focusing on the serotonin transporter gene, which has been suggested to be associated with the gene-environmental interaction in bipolar disorder. Furthermore, I tried to develop a biomarker for detecting underdiagnosed patients with bipolar disorder. I performed high throughput genotyping of 5HTTLPR using DNA derived from peripheral blood of about 1500 healthy elderly subjects. As a result, there was no association between 5HTTLPR and depressive symptoms. Then, I performed comprehensive DNA methylation analysis using DNA derived from peripheral blood of 3 elderly healthy subjects and 4 bipolar disorder patients, and identified the differences of DNA methylation in 56453 genes.

Free Research Field

精神疾患におけるエピジェネティクス

Academic Significance and Societal Importance of the Research Achievements

本研究では、大規模なコホートサンプルを用いて詳細なgenotypingを行うことで、高齢健常者における5HTTLPRと抑うつ症状の関連についての知見を得ることができた。今後はセロトニントランスポーター（SLC6A4）遺伝子のDNAメチル化レベルを測定し、高齢健常者における抑うつ症状とSLC6A4のゲノム・エピゲノム状態の関連を明らかにし、高齢発症の気分障害患者との比較を行うことで、高齢発症の気分障害におけるゲノム・エピゲノム要因について検討する。また、高齢の双極性障害患者におけるエピゲノムバイオマーカーの開発を試みることで、高齢発症の気分障害における分子病態の異種性について検討を行う。