2020 Fiscal Year Final Research Report

Identification of susceptibility genes for type 1 diabetes: whole-exome sequence analysis in rare multiplex families in Japanese

Research Project

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Project/Area Number	18K08530
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 54040:Metabolism and endocrinology-related
Research Institution	Kindai University
Principal Investigator	IKEGAMI Hiroshi 近畿大学, 医学部, 教授 (20221062)
Co-Investigator(Kenkyū-buntansha)	馬場谷成近畿大学, 医学部, 講師 (10449837) 廣峰義久近畿大学, 医学部, 講師 (30460851) 川畑由美子近畿大学, 医学部, 准教授 (80423185) 能宗伸輔近畿大学, 医学部, 准教授 (90460849)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	１型糖尿病 / 遺伝子 / 分子遺伝学 / 次世代シークエンス / 濃厚家系 / ゲノムワイド関連解析 / rare variant / common variant
Outline of Final Research Achievements	To clarify pathogenesis of type 1 diabetes for the development of effective methods for prediction, prevention and cure of type 1 diabetes, we performed molecular genetic analysis of type 1 diabetes by using two approaches. 1) Common variants: genome-wide association study on fulminant type 1 diabetes, 2) Rare variants: whole-exome sequencing in rare multiplex families with type 1 diabetes in Japanese population. GWAS identified two loci associated with fulminant type 1 diabetes with genome-wide significance: HLA on chromosome 6 and CSAD/lnc-ITGB7-1 on chromosome 12q13.13. In multiplex families, existence of two categories of susceptibility genes, genes specific to each family and genes common in multiple families, were found to be present, indicating the importance of precision medicine based on susceptibility genes in each family.
Free Research Field	糖尿病学
Academic Significance and Societal Importance of the Research Achievements	欧米ではほとんど認めない我が国固有の劇症１型糖尿病のGWASで今回初めて同定した遺伝子は、１型糖尿病の劇症化や日本人固有の膵β細胞脆弱性に関する情報を提供する。また我が国では極めて稀な１型糖尿病濃厚発症家系におけるrare variantの同定は寄与率の高い遺伝子の機能解析を通じて１型糖尿病発症の根本に関する基盤情報を提供する。これらの成果は１型糖尿病の予知・予防・根治に不可欠の基盤情報であり、１型糖尿病の根本解決に資することが期待される。