Genome-Wide Association Studies in Glioma

Kinnersley, Ben; Houlston, Richard S.; Bondy, Melissa L.

doi:10.1158/1055-9965.epi-17-1080

Cited by 38 publications

(38 citation statements)

References 128 publications

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“…Comparing our results with previously identified GWAS associations (noted in a review conducted by Kinnersley et al 20 ) revealed that RETREG2 (FAM134A) , FAM178B and MVB12B ( FAM125B ) are putative novel genes implicated in glioma risk that are not also located on a known glioma risk locus and formed part of our main results. The remaining results have been previously implicated in glioma risk through GWAS associations or are located on a known susceptibility locus.…”

Section: Resultssupporting

confidence: 87%

Transcriptome-wide Mendelian randomization study prioritising novel tissue-dependent genes for glioma susceptibility

Robinson

Martin

Tsavachidis

et al. 2021

Sci Rep

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Genome-wide association studies (GWAS) have discovered 27 loci associated with glioma risk. Whether these loci are causally implicated in glioma risk, and how risk differs across tissues, has yet to be systematically explored. We integrated multi-tissue expression quantitative trait loci (eQTLs) and glioma GWAS data using a combined Mendelian randomisation (MR) and colocalisation approach. We investigated how genetically predicted gene expression affects risk across tissue type (brain, estimated effective n = 1194 and whole blood, n = 31,684) and glioma subtype (all glioma (7400 cases, 8257 controls) glioblastoma (GBM, 3112 cases) and non-GBM gliomas (2411 cases)). We also leveraged tissue-specific eQTLs collected from 13 brain tissues (n = 114 to 209). The MR and colocalisation results suggested that genetically predicted increased gene expression of 12 genes were associated with glioma, GBM and/or non-GBM risk, three of which are novel glioma susceptibility genes (RETREG2/FAM134A, FAM178B and MVB12B/FAM125B). The effect of gene expression appears to be relatively consistent across glioma subtype diagnoses. Examining how risk differed across 13 brain tissues highlighted five candidate tissues (cerebellum, cortex, and the putamen, nucleus accumbens and caudate basal ganglia) and four previously implicated genes (JAK1, STMN3, PICK1 and EGFR). These analyses identified robust causal evidence for 12 genes and glioma risk, three of which are novel. The correlation of MR estimates in brain and blood are consistently low which suggested that tissue specificity needs to be carefully considered for glioma. Our results have implicated genes yet to be associated with glioma susceptibility and provided insight into putatively causal pathways for glioma risk.

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Section: Resultssupporting

confidence: 87%

Transcriptome-wide Mendelian randomization study prioritising novel tissue-dependent genes for glioma susceptibility

Robinson

Martin

Tsavachidis

et al. 2021

Sci Rep

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“…Gliomas account for over 80% of all fatal central nervous system (CNS) malignancy [ 1 ] and are the leading cause of cancer‐related mortality among children [ 2 ] and adults aged below 34 years. [ 3 ] Based on histological properties, gliomas are classified into four classes (grades I–IV), in which grade IV, commonly referred to as glioblastoma (GBM), is the most malignant form with an overall mean survival rate of 12–17 months from diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Transformation: The Rosetta Stone of Glioblastoma Pathogenesis and Therapy Resistance

Azam

Tannous

2020

Advanced Science

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Despite decades of research, glioblastoma (GBM) remains invariably fatal among all forms of cancers. The high level of inter-and intratumoral heterogeneity along with its biological location, the brain, are major barriers against effective treatment. Molecular and single cell analysis identifies different molecular subtypes with varying prognosis, while multiple subtypes can reside in the same tumor. Cellular plasticity among different subtypes in response to therapies or during recurrence adds another hurdle in the treatment of GBM. This phenotypic shift is induced and sustained by activation of several pathways within the tumor itself, or microenvironmental factors. In this review, the dynamic nature of cellular shifts in GBM and how the tumor (immune) microenvironment shapes this process leading to therapeutic resistance, while highlighting emerging tools and approaches to study this dynamic double-edged sword are discussed.

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“…Therefore, some researchers have focused on the association between genetic polymorphisms and glioma risk and found a series of susceptible genes. 13 To our best knowledge, our present study is the first meta-analysis to evaluate the association between ACE I/D polymorphism and glioma risk. The results suggested that ACE I/D polymorphism might not be involved in the development of glioma.…”

Section: Discussionmentioning

confidence: 87%

The genetic polymorphisms of angiotensin converting enzyme insertion/deletion and glioma susceptibility: A meta-analysis

Sun

Fang

et al. 2020

J Renin Angiotensin Aldosterone Syst

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Objective: The previous studies on angiotensin converting enzyme (ACE) insertion/deletion (I/D) genetic polymorphism and glioma risk were inconsistent. Therefore, we performed a meta-analysis to assess the association between ACE I/D polymorphisms and glioma risk. Methods and Results: In total, four populations (1110 cases and 1335 controls) on ACE I/D polymorphism were included. Overall, the meta-analysis demonstrated no significant association between ACE I/D polymorphism and glioma risk. In addition, the analysis of the association of ACE I/D polymorphism and clinical grade also showed no significant association. Conclusion: Our meta-analysis didn’t find a significant association between ACE I/D polymorphism glioma risk. However, further studies with larger sample size and more ethnic groups are required to confirm the results.

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Genome-Wide Association Studies in Glioma

Cited by 38 publications

References 128 publications

Transcriptome-wide Mendelian randomization study prioritising novel tissue-dependent genes for glioma susceptibility

Transcriptome-wide Mendelian randomization study prioritising novel tissue-dependent genes for glioma susceptibility

Mesenchymal Transformation: The Rosetta Stone of Glioblastoma Pathogenesis and Therapy Resistance

The genetic polymorphisms of angiotensin converting enzyme insertion/deletion and glioma susceptibility: A meta-analysis

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