Identification and functional analysis of noncoding SNPs causative for genetic disorders

2020 Fiscal Year Final Research Report

• Project/Area Number: 18KT0024
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Complex Systems Disease Theory
• Research Institution: Kyoto University (2020); Kyushu University (2018-2019)
• Principal Investigator: OKi Shinya 京都大学, 医学研究科, 特定准教授 (90452713)
• Project Period (FY): 2018-07-18 – 2021-03-31
• Keywords: GWAS / SNP / ChIP-seq / 転写因子

Outline of Final Research Achievements

GWAS and other case-control studies have identified many disease-associated single nucleotide polymorphisms (marker SNPs). However, since about 90% of disease-associated marker SNPs are located in non-coding regions, it is very difficult to understand the causal relationship between SNPs, which genes they affect, and why they lead to diseases. In this study, we focused on SNPs in non-coding regions that are associated with diseases, and aimed to elucidate the disease process caused by them. As a result, we identified a region where multiple transcription factors involved in immunity and inflammation bind within the linkage disequilibrium region of disease-related SNPs in the non-coding region.

Free Research Field

統合ゲノミクス

Academic Significance and Societal Importance of the Research Achievements

本研究はこれまで見過ごされてきたnon-coding領域のSNPに着目し、転写因子結合情報をフル活用してそのcausal SNPの同定を目指すため、統計遺伝学を駆使した従来のfine-mappingとは大きく異なるアプローチである。本研究の成果は罹患リスクを予測するためのマーカとしてそのまま用いることができるため、coding領域に偏っていた従来の予測精度を飛躍的に引き上げることが期待される。