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This study examines how genetic risk scores (GRS) affect clinical characteristics and mortality in patients with ischemic stroke.

February 14, 2026Frontiers in Neurology0 citationsOpen Access

Genetic risk impacts stroke mortality and pathogenesis in patients with ischemic stroke: a cohort study of BioBank Japan

TSTakashi ShimoyamaNippon Medical School YKYoichiro KamataniThe University of Tokyo KMKoichi MatsudaThe University of Tokyo

Key Points

This study examines how genetic risk scores (GRS) affect clinical characteristics and mortality in patients with ischemic stroke.
Cohort study design involving participants from the BioBank Japan (BBJ) database.
Conducted GWAS on 19,702 ischemic stroke patients and 159,610 controls.
Generated GRS using 29 stroke risk SNPs identified in previous studies.
Employed multivariate logistic regression to assess comorbidities and stroke etiology related to GRS.
Utilized Cox proportional hazard model to analyze mortality risk associated with GRS.
Higher odds ratios (OR) for atrial fibrillation observed with Intermediate GRS (1.59) and High GRS (2.12) compared to Low GRS.
Significantly elevated ORs for cardioembolism in Intermediate (1.31) and High GRS (1.44) groups versus Low GRS.
In a median follow-up of 10 years, mortality risk was significantly higher in High GRS (HR 1.27) compared to Low GRS.

Abstract

Background Previous multi-ancestry genome-wide association studies (GWAS) of stroke reported 32 stroke risk loci in the MEGASTROKE study. Most studies on the genetic risk score (GRS) of stroke have reported a predominance in the European general population. We aimed to explore the association among GRS, clinical characteristics, and mortality in patients with ischemic stroke registered in the BioBank Japan (BBJ) database. Methods This is a cohort study of BBJ participants. The project participants were recruited between June 2003 and March 2018. We conducted a GWAS for stroke in 19,702 Japanese patients with ischemic stroke and 159,610 controls. GRS was generated using 29 stroke risk single nucleotide polymorphisms (SNPs) from 32 stroke-related loci identified in the MEGASTROKE. A multivariate logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for comorbidities and stroke etiology across the GRS. The Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% CIs for mortality associated with GRS. Results The ORs for atrial fibrillation were significantly higher in those at Intermediate GRS 20–80th percentile of GRS; ORs 1.59 (1.25–1.90) and High GRS top 20th percentile of GRS; ORs 2.12 (1.69–2.67) after a full adjustment than in those at Low GRS (bottom 20th percentile of GRS). Regarding stroke etiology, the ORs for cardioembolism were significantly higher in those at Intermediate GRS ORs 1.31 (1.04–1.61) and High GRS ORs 1.44 (1.13–1.89) than in those at Low GRS. During a median follow-up of 10.0 years, the risk of stroke mortality was significantly higher in those at High GRS HRs 1.27 (1.04–1.56) than in those at Low GRS in a fully adjusted model. Conclusion In Japanese, a higher GRS was significantly associated with atrial fibrillation, cardioembolism, and stroke mortality. Our findings suggest that the GRS may predict the risk of stroke mortality and provide insights into the pathogenesis of stroke.

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