Prevalence and clinical impact of JAK2-CHIP: Association with Parkinsonism and hematologic changes in a population cohort.

BACKGROUND

JAK2V617F-associated clonal hematopoiesis of indeterminate potential (JAK2-CHIP) has been implicated in cardiovascular disease through inflammatory and thrombotic mechanisms. However, its role in microthromboembolism-related events (miTE-REs), particularly neurodegenerative disorders, remains underexplored.

METHODS

In this retrospective cohort study, we screened 1768 individuals from a health screening population for JAK2V617F using a high-sensitivity qCAST-Duplex PCR assay. To enhance efficiency, we employed a pooled PCR strategy: genomic DNA from 10 samples was combined per reaction. Given the assay's detection limit of 0.01 %, this approach allowed identification of any individual sample with a mutant allele burden (AB) > 0.1 %. Positive pools were deconvoluted and tested individually. Clinical data were analyzed to assess associations between JAK2-CHIP and miTE-REs, including Parkinsonism, dementia, Alzheimer's disease, heart failure, and avascular necrosis. Temporal changes in AB were evaluated in participants with serial blood samples.

RESULTS

JAK2-CHIP was identified in 32 individuals (1.8 %), with prevalence increasing with age. Carriers had a significantly higher prevalence of Parkinsonism than non-carriers (15.6 % vs. 6.3 %, p = 0.035). Carriers with AB ≥1 % had elevated platelet and basophil counts, suggesting subclinical myeloid lineage activation. Among those with serial data, 22.7 % showed clonal expansion, though none developed hematologic malignancy.

CONCLUSION

JAK2-CHIP is associated with increased prevalence of Parkinsonism in otherwise healthy individuals, possibly via microvascular or inflammatory pathways. Elevated platelet and basophil counts among carriers support early functional consequences of this mutation. These findings highlight the clinical relevance of detecting JAK2-CHIP in general populations and underscore its potential as a biomarker for neurologic risk stratification and longitudinal monitoring.