Genomic structural variation analysis of diabetic kidney disease using whole genome sequencing data accompanied with functional analysis

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K17275
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Sugawara Yuka 東京大学, 医学部附属病院, 特任助教 (70841881)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: whole genome sequence / 糖尿病性腎臓病 / 構造多型

Outline of Final Research Achievements

Whole genome sequencing data of 79 cases of diabetic kidney disease were analyzed with clinical information to detect single nucleotide polymorphisms, short In/Del, and structural variations associated with disease onset and/or clinical phenotype. The frequency of single nucleotide polymorphisms and short In/Del classified as pathogenic/likely pathogenic by the ACMG criteria was compared with that of previously reported cases, and the frequency was found to be higher than past reports. For structural variations, 12 variations related to the phenotype of diabetic kidney disease were identified. These frequency studies are being requested for a large cohort.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、生活習慣病とされる本邦糖尿病性腎臓病症例において、腎疾患・糖尿病・炎症等に関係のあるpathogenic/likely pathogenicな多型が相当数発見され、本疾患の治療においては生活習慣の是正に加え、遺伝学的背景からのアプローチも今後必要とされることが示唆された。また、疾患原性のある多型を保持する症例を見分けることは臨床病型からは難しいことも示唆された。さらに、これまで本疾患に対する構造多型の関与は明らかではなかったが、疾患の表現型に相関する構造多型が検出されたことから、構造多型の疾患への寄与も示唆される結果を得た。