Predicting mortality among ischemic stroke patients using pathways-derived polygenic risk scores

We aim to determine whether ischemic stroke(IS)-related PRSs are also associated with and further predict 3-year all-cause mortality. 1756 IS patients with European ancestry were randomly split into training (n = 1226) and testing (n = 530) groups with 3-year post-event observations. Univariate Cox...

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Bibliographic Details
Published in:Scientific reports Vol. 12; no. 1; pp. 12358 - 15
Main Authors: Li, Jiang, Chaudhary, Durgesh, Griessenauer, Christoph J., Carey, David J., Zand, Ramin, Abedi, Vida
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 19.07.2022
Nature Publishing Group
Nature Portfolio
Subjects:
631/114/2413
631/208/205/2138
692/617/375/1370/534
Apoptosis
Endothelial cells
Humanities and Social Sciences
Ischemia
Mortality
multidisciplinary
Patients
Prediction models
Risk factors
Risk groups
Science
Science (multidisciplinary)
Stroke
ISSN:2045-2322, 2045-2322
Online Access:Get full text
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Summary:We aim to determine whether ischemic stroke(IS)-related PRSs are also associated with and further predict 3-year all-cause mortality. 1756 IS patients with European ancestry were randomly split into training (n = 1226) and testing (n = 530) groups with 3-year post-event observations. Univariate Cox proportional hazards regression model (CoxPH) was used for primary screening of individual prognostic PRSs. Only the significantly associated PRSs and clinical risk factors with the same direction for a causal relationship with IS were used to construct a multivariate CoxPH. Feature selection was conducted by the LASSO method. After feature selection, a prediction model with 11 disease-associated pathway-specific PRSs outperformed the base model, as demonstrated by a higher concordance index (0.751, 95%CI [0.693–0.809] versus 0.729, 95%CI [0.676–0.782]) in the testing sample. A PRS derived from endothelial cell apoptosis showed independent predictability in the multivariate CoxPH (Hazard Ratio = 1.193 [1.027–1.385], p  = 0.021). These PRSs fine-tuned the model by better stratifying high, intermediate, and low-risk groups. Several pathway-specific PRSs were associated with clinical risk factors in an age-dependent manner and further confirmed some known etiologies of IS and all-cause mortality. In conclusion, Pathway-specific PRSs for IS are associated with all-cause mortality, and the integrated multivariate risk model provides prognostic value in this context.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-16510-x