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Meta-Analysis
. 2021 Aug 2;23(8):1304-1314.
doi: 10.1093/neuonc/noab072.

Partitioned glioma heritability shows subtype-specific enrichment in immune cells

Quinn T Ostrom  1 , Jacob Edelson  2   3 , Jinyoung Byun  1   2 , Younghun Han  1   2 , Ben Kinnersley  4 , Beatrice Melin  5 , Richard S Houlston  4 , Michelle Monje  6 ; GLIOGENE Consortium; Kyle M Walsh  7   8 , Christopher I Amos  1   2 , Melissa L Bondy  1   9
Collaborators, Affiliations
Meta-Analysis

Partitioned glioma heritability shows subtype-specific enrichment in immune cells

Quinn T Ostrom et al. Neuro Oncol. .

Abstract

Background: Epidemiological studies of adult glioma have identified genetic syndromes and 25 heritable risk loci that modify individual risk for glioma, as well increased risk in association with exposure to ionizing radiation and decreased risk in association with allergies. In this analysis, we assess whether there is a shared genome-wide genetic architecture between glioma and atopic/autoimmune diseases.

Methods: Using summary statistics from a glioma genome-wide association studies (GWAS) meta-analysis, we identified significant enrichment for risk variants associated with gene expression changes in immune cell populations. We also estimated genetic correlations between glioma and autoimmune, atopic, and hematologic traits using linkage disequilibrium score regression (LDSC), which leverages genome-wide single-nucleotide polymorphism (SNP) associations and patterns of linkage disequilibrium.

Results: Nominally significant negative correlations were observed for glioblastoma (GB) and primary biliary cirrhosis (rg = -0.26, P = .0228), and for non-GB gliomas and celiac disease (rg = -0.32, P = .0109). Our analyses implicate dendritic cells (GB pHM = 0.0306 and non-GB pHM = 0.0186) in mediating both GB and non-GB genetic predisposition, with GB-specific associations identified in natural killer (NK) cells (pHM = 0.0201) and stem cells (pHM = 0.0265).

Conclusions: This analysis identifies putative new associations between glioma and autoimmune conditions with genomic architecture that is inversely correlated with that of glioma and that T cells, NK cells, and myeloid cells are involved in mediating glioma predisposition. This provides further evidence that increased activation of the acquired immune system may modify individual susceptibility to glioma.

Keywords: allergies; autoimmune disease; genetic architecture; glioma; heritability.

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Figures

Fig. 1
Fig. 1
−log10(P) for individual-specific tissue sample and harmonic mean P within tissue categories for (A) GB and (B) non-GB based on GTex reference data (dotted line indicates P < .05). Abbreviation: GB: glioblastoma.
Fig. 2
Fig. 2
log10(P) by individual cell line sample and harmonic mean P within immune cell category for (A) GB and (B) non-GB based on ImmGen reference data (dotted line indicates P < .05). Abbreviation: GB: glioblastoma.
Fig. 2
Fig. 2
log10(P) by individual cell line sample and harmonic mean P within immune cell category for (A) GB and (B) non-GB based on ImmGen reference data (dotted line indicates P < .05). Abbreviation: GB: glioblastoma.
Fig. 3
Fig. 3
Estimated heritability for autoimmune and atopic phenotypes, and genetic correlation between atopic and autoimmune phenotypes and glioma subgroups, dotted line indicates P < .05.
See this image and copyright information in PMC

References

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