Leveraging Polygenic Risk Score for Elucidating Novel Disease Mechanisms in Hypertrophic Cardiomyopathy

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17110
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kanazawa University
• Principal Investigator: Akihiro Nomura 金沢大学, 融合科学系, 准教授 (30707542)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 肥大型心筋症 / 多遺伝子リスクスコア / バイオインフォマティクス

Outline of Final Research Achievements

In this study, we conducted a research for hypertrophic cardiomyopathy (HCM) that could occur through the combination of multiple genetic variants using a polygenic risk score (PRS) for inter-ventricular septal thickness (PRS-IVS), especially targeting HCM patients in whom the cause could not be identified by conventional genetic screening for monogenic causal variants. Firstly, we established the method for calculating PRS-IVS. Secondly, we showed that both the HCM causal variant carrier group and the HCM causal variant non-carrier group had significantly higher PRS-IVS values compared to the control group. On the other hand, no significant difference in PRS-IVS was observed between causal variant carriers and non-carriers among patients with HCM. Furthermore, no correlation was found between PRS-IVS and the actual IVS values of each group.

Free Research Field

循環器学

Academic Significance and Societal Importance of the Research Achievements

今回の研究では、肥大型心筋症(HCM)の臨床的診断基準に用いられている心室中隔壁厚(IVS)に対する多遺伝子リスクスコア(PRS-IVS)を、日本人の公開ゲノム解析データ(BioBank Japan)を用いて計算する方法を確立した。また、非HCM患者(対照群)に対して、HCM群は原因遺伝子変異の有無に関わらずPRS-IVSが有意に高値であることを初めて明らかにした。今後も、多数の遺伝子が関与してHCMの形態学的特徴を呈しうる患者の同定、ならびにその疾患機序の解明に向け、さらなる研究が必要である。