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Recurrent Stroke Prediction by Applying a Stroke Polygenic Risk Score in the Japanese Population.

Naoki Kojima1, Masaru Koido1, Yunye He1

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A novel polygenic risk score (PRS) effectively predicts recurrent stroke in Japanese individuals, particularly those without hypertension. This genetic tool aids in personalized stroke recurrence prevention strategies.

Keywords:
Japangenetic risk scorehypertensionrisk factorsstroke

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Area of Science:

  • Genetics
  • Cardiovascular Diseases
  • Epidemiology

Background:

  • Current polygenic risk scores (PRS) demonstrate limited efficacy in predicting recurrent stroke.
  • There is a need for improved genetic risk prediction models for stroke recurrence.
  • Optimizing PRS for specific populations, like Japanese individuals, may enhance predictive performance.

Purpose of the Study:

  • To evaluate the predictive performance of a newly developed polygenic risk score (metaGRS) for stroke recurrence in a Japanese population.
  • To compare the efficacy of the optimized metaGRS against existing PRSs for predicting recurrent stroke.
  • To investigate the association of metaGRS with stroke recurrence, stratified by risk factors like hypertension.

Main Methods:

  • Derived and optimized PRSs using 10-fold cross-validation in the BioBank Japan first cohort (BBJ1).
  • Integrated multiple trait-optimized PRSs using a meta-scoring approach (metaGRS).
  • Validated metaGRS association with stroke and recurrent stroke in an independent BioBank Japan second cohort (BBJ2), analyzing risk factor stratification and index event bias.

Main Results:

  • The optimized metaGRS was significantly associated with stroke recurrence in the BBJ2 cohort (adjusted odds ratio per SD, 1.18; P=0.044).
  • Published PRSs showed no significant correlation with stroke recurrence.
  • The high metaGRS group without hypertension exhibited a substantially higher risk of recurrent stroke (adjusted odds ratio, 2.24; P=0.032), while no association was found in the hypertension group.

Conclusions:

  • The developed metaGRS effectively predicts stroke recurrence in an independent Japanese cohort.
  • MetaGRS shows particular promise in identifying Japanese individuals without hypertension at higher risk for stroke recurrence.
  • These findings support the use of genetically informed risk stratification for personalized stroke recurrence prevention.