Abstract WMP105: Association of Comorbidities, Stroke Etiology, and Polygenic Risk Score in Japanese Ischemic Stroke Patients

Abstract

Background: Previous trans-ancestry genome-wide association studies (GWAS) of stroke reported 32 stroke risk loci, which were conducted predominantly in populations of European ancestry. The aim of this study was to examine the association of comorbidities, stroke etiology, and polygenic risk score (PRS) for stroke in the Japanese population. Methods: A total of 19702 ischemic stroke patients (n= 12241 male and n= 7261 female, median age 71 years old) were analyzed. We selected 19 significant stroke loci from a set of 32 stroke-related genes to construct the PRS in the Japanese population. The multivariate logistic regression model was conducted to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) for comorbidity and stroke etiology across the PRS. Results: Compared with the lowest quintile PRS, the ORs (95%CIs) of atrial fibrillation/flutter at the top PRS quintile was significantly higher independently from traditional stroke risk factors (ORs, 2.13; 95%CIs 1.69-2.68). This significant association remained through continuous PRS (ORs, 1.59; 95%CIs 1.10-2.31). Other traditional stroke risk factors were not significantly associated with increased PRS. Similarly, we also investigated the association between the PRS and stroke subtype in patients with identified stroke etiology based on the TOAST criteria (n=6608). Continuous PRS was significantly higher in patients with cardioembolism by multivariate logistic analysis (ORs 1.45; 95%CIs 1.14-1.85). Conversely, continuous PRS was significantly lower in patients with small vessel occlusion (ORs 0.85; 95%CIs 0.73-0.98). Conclusion: In Japanese ischemic stroke patients, PRS for stroke was significantly associated with atrial fibrillation/flutter and cardioembolism. Our findings suggest that the importance of a PRS for stroke may be helpful for identifying high-risk sources of cardioembolism including atrial fibrillation in the Japanese population.