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Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival

Author

Listed:
  • Linda Kachuri

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Geno A. Guerra

    (University of California San Francisco
    University of California San Francisco)

  • Taishi Nakase

    (Stanford University School of Medicine)

  • George A. Wendt

    (University of California San Francisco)

  • Helen M. Hansen

    (University of California San Francisco)

  • Annette M. Molinaro

    (University of California San Francisco
    University of California San Francisco)

  • Paige Bracci

    (University of California San Francisco)

  • Lucie McCoy

    (University of California San Francisco)

  • Terri Rice

    (University of California San Francisco)

  • John K. Wiencke

    (University of California San Francisco
    University of California San Francisco)

  • Jeanette E. Eckel-Passow

    (Mayo Clinic)

  • Robert B. Jenkins

    (Mayo Clinic)

  • Margaret Wrensch

    (University of California San Francisco)

  • Stephen S. Francis

    (University of California San Francisco
    University of California San Francisco
    University of California San Francisco)

Abstract

Glioma is a highly fatal and heterogeneous brain tumor with few known risk factors. Our study examines genetically predicted variability in blood cell indices in relation to glioma risk and survival in 3418 cases and 8156 controls. We find that increased platelet to lymphocyte ratio (PLR) confers an increased risk of glioma (odds ratio (OR) = 1.25, p = 0.005), especially tumors with isocitrate dehydrogenase (IDH) mutations (OR = 1.38, p = 0.007) and IDHmut 1p/19q intact (IDHmut-intact OR = 1.53, p = 0.004) tumors. Genetically inferred increased counts of lymphocytes (IDHmut-intact OR = 0.70, p = 0.004) and neutrophils (IDHmut OR = 0.69, p = 0.019; IDHmut-intact OR = 0.60, p = 0.009) show inverse associations with risk, which may reflect enhanced immune-surveillance. Considering survival, we observe higher mortality risk in patients with IDHmut 1p/19q with genetically predicted increased counts of lymphocytes (hazard ratio (HR) = 1.65, 95% CI: 1.24–2.20), neutrophils (HR = 1.49, 1.13–1.97), and eosinophils (HR = 1.59, 1.18–2.14). Polygenic scores for blood cell traits are also differentially associated with 17 tumor immune microenvironment features in a subtype-specific manner, including signatures related to interferon signaling, PD-1 expression, and T-cell/Cytotoxic responses. Our findings highlight immune-mediated susceptibility mechanisms with potential disease management implications.

Suggested Citation

  • Linda Kachuri & Geno A. Guerra & Taishi Nakase & George A. Wendt & Helen M. Hansen & Annette M. Molinaro & Paige Bracci & Lucie McCoy & Terri Rice & John K. Wiencke & Jeanette E. Eckel-Passow & Robert, 2025. "Genetic predisposition to altered blood cell homeostasis is associated with glioma risk and survival," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-55919-6
    DOI: 10.1038/s41467-025-55919-6
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    References listed on IDEAS

    as
    1. Frank Dudbridge & Richard J. Allen & Nuala A. Sheehan & A. Floriaan Schmidt & James C. Lee & R. Gisli Jenkins & Louise V. Wain & Aroon D. Hingorani & Riyaz S. Patel, 2019. "Adjustment for index event bias in genome-wide association studies of subsequent events," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    2. Chris Wallace, 2021. "A more accurate method for colocalisation analysis allowing for multiple causal variants," PLOS Genetics, Public Library of Science, vol. 17(9), pages 1-11, September.
    3. Gibran Hemani & Kate Tilling & George Davey Smith, 2017. "Orienting the causal relationship between imprecisely measured traits using GWAS summary data," PLOS Genetics, Public Library of Science, vol. 13(11), pages 1-22, November.
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