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Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
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Predicting mortality among ischemic stroke patients using pathways-derived polygenic risk scores.

Jiang Li1, Durgesh Chaudhary2, Christoph J Griessenauer2,3

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Polygenic risk scores (PRSs) for ischemic stroke (IS) predict 3-year all-cause mortality. An integrated risk model using pathway-specific PRSs improves mortality prediction in IS patients.

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Area of Science:

  • Genetics
  • Cardiovascular Diseases
  • Epidemiology

Background:

  • Ischemic stroke (IS) poses a significant health burden, with limited understanding of long-term mortality predictors.
  • Polygenic risk scores (PRSs) are emerging tools for assessing genetic predisposition to complex diseases.

Purpose of the Study:

  • To investigate if IS-related PRSs are associated with and can predict 3-year all-cause mortality.
  • To develop and validate a multivariate risk prediction model incorporating pathway-specific PRSs for IS patients.

Main Methods:

  • A cohort of 1756 IS patients of European ancestry was divided into training and testing sets.
  • Cox proportional hazards regression and LASSO feature selection were employed to build a multivariate prediction model.
  • The model's performance was evaluated using the concordance index (C-index).

Main Results:

  • A prediction model integrating 11 pathway-specific PRSs demonstrated superior performance (C-index=0.751) compared to a base model (C-index=0.729) in the testing set.
  • A PRS associated with endothelial cell apoptosis independently predicted mortality (HR=1.193, p=0.021).
  • The PRSs effectively stratified patients into distinct risk groups for mortality.

Conclusions:

  • Pathway-specific PRSs for IS are significantly associated with 3-year all-cause mortality.
  • An integrated multivariate risk model incorporating these PRSs offers valuable prognostic information for IS survivors.
  • The findings highlight the potential of polygenic risk prediction in managing long-term outcomes after ischemic stroke.