Integrated genome-wide association study in sepsis

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03779
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Chiba University
• Principal Investigator: Nakada Taka-aki 千葉大学, 大学院医学研究院, 教授 (20375794)
• Co-Investigator(Kenkyū-buntansha): 関根 章博 千葉大学, 大学院医学研究院, 特任教授 (30425631) ; 島田 忠長 千葉大学, 医学部附属病院, 助教 (40436423)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 敗血症 / GWAS / 遺伝子多型

Outline of Final Research Achievements

A Japanese sepsis cohort (approximately 800 cases) was collected. Genomic DNA from the collected sepsis patients was extracted, and genotyping of 2.5 million genome-wide SNPs was performed using SNP arrays. Quality control analysis was performed to finalize the SNPs dataset for GWAS analysis. Using these comprehensive SNP genotyping data, we performed a GWAS analysis with death as the outcome, and the GWAS results showed peaks at four loci associated with sepsis mortality in a Manhattan plot. We are investigating the results of previous reports and other cohort analyses for these loci. A GWAS study using non-synonymous SNPs in the Canadian sepsis cohort found an association between sepsis and the SVEP1 polymorphism, and we are conducting experiments and analysis of the relationship between SVEP1 and the pathogenesis of sepsis in mice.

Free Research Field

救急集中治療医学

Academic Significance and Societal Importance of the Research Achievements

敗血症は依然致死率が高く、死亡者数は近年増加傾向である。遺伝的要因が敗血症による死亡に与える影響が大きいことが報告されている。全ゲノムを網羅的に解析するゲノムワイド関連解析は既存の知見に制限を受けずに新しい発見を得られる可能性のある革新的な研究方法であり、敗血症の網羅遺伝的解析は未だ少ない。本研究では新たに4箇所の関連遺伝子座を発見しており、大きな学術的意義が高い。またカナダ敗血症コホートのnon-synonymous SNPを用いたGWAS研究で敗血症とのSVEP1遺伝子多型の関連が発見されているが、敗血症との病態との関連は解明されておらず、明らかとすることは大きな意義がある。