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

Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Monday, February 16, 2026

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

Don't you dare use genetic risk as an excuse for not changing the status quo and getting these people recovered! Excuses won't be tolerated, you're fired! Leaders would solve such a problem; obviously you have NO LEADERSHIP potential!

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

Takashi Shimoyama¹^*^†

Yoichiro Kamatani²^†

Koichi Matsuda³^†

Hiroki Yamaguchi⁴^†

Kazumi Kimura¹^†

¹Department of Neurology, Nippon Medical School, Tokyo, Japan
²Laboratory of Complex Trait Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
³Department of Computational Biology and Medical Science, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
⁴Department of Hematology, Nippon Medical School, Tokyo, Japan

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.

Introduction

Stroke is the second-leading cause of death and the primary cause of neurological disability worldwide (1, 2). Stroke is caused by a complex interplay of environmental and traditional risk factors, including older age, hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, chronic kidney disease, and smoking (3). Besides conventional clinical risk factors, the genetic contribution to the development of stroke is also widely recognized (4). Twin and family history studies suggest genetic factors are responsible for some of this unexplained risk for stroke. The heritability estimates were 0.32 for the liability to stroke death and 0.17 for stroke hospitalization or stroke death (5).

Over the last decades, several genome-wide association studies (GWAS) have identified genetic variants associated with stroke in different ethnic populations (6–11). Previous multi-ancestry GWAS of 52,000 subjects in predominantly European-ancestry groups have identified 32 loci associated with stroke and stroke subtypes (MEGASTROKE study) (11). Recent work has highlighted the potential of the genetic risk score (GRS) based on the MEGASTROKE study, which can be evaluated as a risk factor for stroke and used to predict incident stroke events in an independent population (11–16). The risk of incident stroke was higher in those at high genetic risk than in those at low genetic risk (12). The polygenic risk score (PRS) using 3.6 million genetic variants predicts stroke incidents in a population of 12,792 healthy older individuals enrolled in the ASPREE trial (Aspirin in Reducing Events in the Elderly) (13). In a genetic cohort analysis pooling 51,288 subjects with cardiometabolic disease from five cardiovascular clinical trials, GRS using the set of 32 single nucleotide polymorphisms (SNPs) derived from the MEGASTROKE study was a strong, independent predictor of ischemic stroke incidence over a median follow-up period of 2.5 years (14). In the Northern Finland Birth Cohort 1966 of 12,058 children, higher PRS for stroke was associated with the risk for cerebrovascular disease in mid-life in Finnish population. Ischemic stroke (15). Although investigation of genetic risk for stroke has been limited in non-European populations, the Hisayama Study, which involved 3,038 Japanese individuals, reported the PRS for stroke using 350,000 SNPs was significantly associated with stroke incidence during long-term follow-up (median 10.2 years) (16). Most of the advanced literature on genetic risk for stroke has been reported in general populations regardless of ethnicity; however, solid evidence in the relevant literature has not described the clinical significance of genetic risk for stroke in non-European stroke patients.

To address these limitations, we developed a GRS for stroke from a set of 32 stroke risk loci identified in the MEGASTROKE study in Japanese patients with ischemic stroke. We hypothesized that subsets with a higher genetic risk influence stroke mechanisms and mortality compared to those with a lower genetic risk of ischemic stroke. This cohort study aimed to clarify the association between the GRS score, clinical characteristics, and mortality in stroke patients registered in the BioBank Japan (BBJ) database.