Identification of rare genetic variants associated with bipolar disorder and comprehensive analysis to elucidate its pathophysiology

2015 Fiscal Year Final Research Report

• Project/Area Number: 25253072
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Nagoya University
• Principal Investigator: OZAKI Norio 名古屋大学, 医学(系)研究科(研究院), 教授 (40281480)
• Co-Investigator(Renkei-kenkyūsha): IRITANI Syuji 名古屋大学, 大学院医学系研究科, 寄附講座教授 (60191904) ; IIDAKA Tetsuya 名古屋大学, 大学院医学系研究科, 准教授 (70324366) ; ALEKSIC Branko 名古屋大学, 大学院医学系研究科(国際), 特任准教授 (60547511) ; KUNIMOTO Shohko 名古屋大学, 大学院医学系研究科, 特任助教 (30350135) ; KANBA Shigenobu 九州大学, 医学部, 教授 (60312112) ; IWATA Nakao 藤田保健衛生大学, 医学部, 教授 (60312112) ; OKANO Hideyuki 慶應義塾大学, 医学部, 教授 (60312112) ; NODA Yukihiro 名城大学, 薬学部, 教授 (60312112)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 双極性障害 / ゲノムコピー数変異

Outline of Final Research Achievements

We performed a high-resolution genome-wide copy number variation (CNV) analysis on Japanese patients with bipolar disorder (BP). We identified clinically significant CNVs in around 6% of BP patients. Among others, PCDH15 (protocadherin 15) was identified as a promising candidate gene because exonic deletions were observed in three patients. From two BP patients with PCDH15 deletions, we established induced pluripotent stem (iPS) cell lines. We applied genome-modifying technology of CRISPR/Cas9 method and generated the Pcdh15-deficient mice, carrying the NHEJ mutant allele.

Free Research Field

医歯薬学