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Objective <p>Our study aimed to determine the prevalence and clinical phenotypes of <i>JAK2</i> pathogenic mutation carriers in the CNSR-III ischemic stroke (IS) cohort, and to develop a pre-test genetic screening model for identifying high-risk individuals.</p> Methods <p>We performed retrospective characterization of <i>JAK2</i> pathogenic variants using targeted sequencing data in the CNSR-III cohort. Clinical and laboratory characteristics of <i>JAK2</i> V617F mutation carriers and non-carriers were tested in a logistic regression model to identify key features. V617F screening score was developed to predict positive <i>JAK2</i> V617F test results.</p> Results <p>46 cases (0.4%, 46/10428) harbored the <i>JAK2</i> V617F-exclusive mutation. Mutation carriers manifested significantly inferior functional outcomes following stroke relative to non-carriers (adjusted OR 2.74[1.07, 6.49]). Significant predictors of mutation status comprised elevated platelet count (PLT, OR 1.02[1.02, 1.03]), increased hemoglobin concentrations (HGB, OR 1.06 [1.04, 1.08]), and a reduced burden of traditional stroke risk factors, such as history of hypertension (OR 0.24[0.11, 0.52]), smoking history (OR 0.08[0.02, 0.24]), and body mass index (BMI, OR 0.8[0.75, 0.97]). We constructed the <i>JAK2</i> V617F screening score, which efficiently discriminated between carriers and non-carriers (area under the ROC curve, AUC 0.98), achieving sensitivity of 85%, specificity of 94%, and accuracy of 94% for a cut-off score of 3 points. Internal validation confirmed robust performance, with a consistent AUC&#xa0;of 0.98.</p> Conclusions <p>Despite low prevalence (0.4%), <i>JAK2</i> V617F mutation represents a clinically actionable stroke subtype with distinct pathophysiology. The prediction model offers a precision medicine approach, potentially reducing the need for comprehensive genetic testing.</p>

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JAK2 pathogenic variants in ischemic stroke: low prevalence and pre-screening model

  • 期刊论文

  • 发表日期：

    2026年2月7日

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  • Jialu Zhao,
  • Siqi Ge,
  • Shujun Gao,
  • Liting Xue,
  • Yanfeng Shi,
  • Chaoxia Lu,
  • Fang Fang,
  • Hui Wang,
  • Yumei Zhang,
  • Yulin Zhang,
  • Cang Guo,
  • Meng Wang,
  • Yijun Zhang,
  • Manqi Zheng,
  • Qin Xu,
  • Anxin Wang,
  • Hongqiu Gu,
  • Wanlin Zhu,
  • Yong Jiang,
  • Hao Li,
  • Xia Meng,
  • Yongjun Wang,
  • Wei Li

摘要

Objective

Our study aimed to determine the prevalence and clinical phenotypes of JAK2 pathogenic mutation carriers in the CNSR-III ischemic stroke (IS) cohort, and to develop a pre-test genetic screening model for identifying high-risk individuals.

Methods

We performed retrospective characterization of JAK2 pathogenic variants using targeted sequencing data in the CNSR-III cohort. Clinical and laboratory characteristics of JAK2 V617F mutation carriers and non-carriers were tested in a logistic regression model to identify key features. V617F screening score was developed to predict positive JAK2 V617F test results.

Results

46 cases (0.4%, 46/10428) harbored the JAK2 V617F-exclusive mutation. Mutation carriers manifested significantly inferior functional outcomes following stroke relative to non-carriers (adjusted OR 2.74[1.07, 6.49]). Significant predictors of mutation status comprised elevated platelet count (PLT, OR 1.02[1.02, 1.03]), increased hemoglobin concentrations (HGB, OR 1.06 [1.04, 1.08]), and a reduced burden of traditional stroke risk factors, such as history of hypertension (OR 0.24[0.11, 0.52]), smoking history (OR 0.08[0.02, 0.24]), and body mass index (BMI, OR 0.8[0.75, 0.97]). We constructed the JAK2 V617F screening score, which efficiently discriminated between carriers and non-carriers (area under the ROC curve, AUC 0.98), achieving sensitivity of 85%, specificity of 94%, and accuracy of 94% for a cut-off score of 3 points. Internal validation confirmed robust performance, with a consistent AUC of 0.98.

Conclusions

Despite low prevalence (0.4%), JAK2 V617F mutation represents a clinically actionable stroke subtype with distinct pathophysiology. The prediction model offers a precision medicine approach, potentially reducing the need for comprehensive genetic testing.