Abstract 17207: Usefulness of Polygenic Risk Score for Intraventricular Septal Diameter in Patients With Hypertrophic Cardiomyopathy

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Background: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant monogenic disease characterized by thickened heart muscles, particularly at the intraventricular septum (IVS), and an increased risk of arrythmias and sudden death. Recently, in addition to monogenic screening, the polygenic risk score (PRS) has been proposed as a potentially useful tool for risk stratification in several cardiovascular diseases. However, it remains unclear whether PRS is also beneficial for risk stratification of patients with HCM. Methods: We recruited and genotyped HCM patients from the Kanazawa University Mendelian Disease (KUMD) HCM registry and controls from the KUMD non-HCM familial hypercholesterolemia registry. The PRS was calculated from over 3 million genotyped with imputed variants of each participant for IVS diameter (PRS IVS ) using a publicly available summary statistic at the National Bioscience Database Center. We assessed the PRS IVS distributions among the monogenic HCM, causal variant negative HCM, and control groups. We also tested the associations of PRS IVS with the IVS diameters within each group. Results: We evaluated a total of 400 participants (267 HCM patients, including 79 with monogenic HCM and 188 with causal variant negative HCM, and 133 controls) for the analyses. Compared to the controls, PRS IVS was significantly higher in both monogenic HCM (0.12923 in Monogenic HCM vs. 0.09057 in controls, age- and sex-adjusted p = 0.02) and causal variant negative HCM patients (0.11127 in causal variant negative HCM vs. 0.09057 in controls, p = 9.9x10 -4 ). However, no associations were found between PRS IVS and IVS diameters in any of the groups. Conclusions: In this study, both the monogenic HCM and causal variant negative HCM groups demonstrated significantly higher PRS IVS than non-HCM controls. However, we found no evidence to suggest that PRS IVS might be useful for risk stratification in patients with HCM.