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Searching for causal relationships of glioma: a phenome-wide Mendelian randomisation study.

Publication ,  Journal Article
Saunders, CN; Cornish, AJ; Kinnersley, B; Law, PJ; Houlston, RS; Collaborators
Published in: Br J Cancer
January 2021

BACKGROUND: The aetiology of glioma is poorly understood. Summary data from genome-wide association studies (GWAS) can be used in a Mendelian randomisation (MR) phenome-wide association study (PheWAS) to search for glioma risk factors. METHODS: We performed an MR-PheWAS analysing 316 phenotypes, proxied by 8387 genetic variants, and summary genetic data from a GWAS of 12,488 glioma cases and 18,169 controls. Causal effects were estimated under a random-effects inverse-variance-weighted (IVW-RE) model, with robust adjusted profile score (MR-RAPS), weighted median and mode-based estimates computed to assess the robustness of findings. Odds ratios per one standard deviation increase in each phenotype were calculated for all glioma, glioblastoma (GBM) and non-GBM tumours. RESULTS: No significant associations (P < 1.58 × 10-4) were observed between phenotypes and glioma under the IVW-RE model. Suggestive associations (1.58 × 10-4 < P < 0.05) were observed between leukocyte telomere length (LTL) with all glioma (ORSD = 3.91, P = 9.24 × 10-3) and GBM (ORSD = 4.86, P = 3.23 × 10-2), but the association was primarily driven by the TERT variant rs2736100. Serum low-density lipoprotein cholesterol and plasma HbA1C showed suggestive associations with glioma (ORSD = 1.11, P = 1.39 × 10-2 and ORSD = 1.28, P = 1.73 × 10-2, respectively), both associations being reliant on single genetic variants. CONCLUSIONS: Our study provides further insight into the aetiological basis of glioma for which published data have been mixed.

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Published In

Br J Cancer

DOI

EISSN

1532-1827

Publication Date

January 2021

Volume

124

Issue

2

Start / End Page

447 / 454

Location

England

Related Subject Headings

  • Risk Factors
  • Oncology & Carcinogenesis
  • Mendelian Randomization Analysis
  • Humans
  • Glioma
  • Genome-Wide Association Study
  • Genetic Variation
  • Brain Neoplasms
  • 3211 Oncology and carcinogenesis
  • 1117 Public Health and Health Services
 

Citation

APA
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MLA
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Saunders, C. N., Cornish, A. J., Kinnersley, B., Law, P. J., Houlston, R. S., & Collaborators. (2021). Searching for causal relationships of glioma: a phenome-wide Mendelian randomisation study. Br J Cancer, 124(2), 447–454. https://doi.org/10.1038/s41416-020-01083-1
Saunders, Charlie N., Alex J. Cornish, Ben Kinnersley, Philip J. Law, Richard S. Houlston, and Collaborators. “Searching for causal relationships of glioma: a phenome-wide Mendelian randomisation study.Br J Cancer 124, no. 2 (January 2021): 447–54. https://doi.org/10.1038/s41416-020-01083-1.
Saunders CN, Cornish AJ, Kinnersley B, Law PJ, Houlston RS, Collaborators. Searching for causal relationships of glioma: a phenome-wide Mendelian randomisation study. Br J Cancer. 2021 Jan;124(2):447–54.
Saunders, Charlie N., et al. “Searching for causal relationships of glioma: a phenome-wide Mendelian randomisation study.Br J Cancer, vol. 124, no. 2, Jan. 2021, pp. 447–54. Pubmed, doi:10.1038/s41416-020-01083-1.
Saunders CN, Cornish AJ, Kinnersley B, Law PJ, Houlston RS, Collaborators. Searching for causal relationships of glioma: a phenome-wide Mendelian randomisation study. Br J Cancer. 2021 Jan;124(2):447–454.

Published In

Br J Cancer

DOI

EISSN

1532-1827

Publication Date

January 2021

Volume

124

Issue

2

Start / End Page

447 / 454

Location

England

Related Subject Headings

  • Risk Factors
  • Oncology & Carcinogenesis
  • Mendelian Randomization Analysis
  • Humans
  • Glioma
  • Genome-Wide Association Study
  • Genetic Variation
  • Brain Neoplasms
  • 3211 Oncology and carcinogenesis
  • 1117 Public Health and Health Services