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Journal Articles British Journal of Cancer Year : 2020

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

Elizabeth B Claus
  • Function : Author
Dora Il’yasova
  • Function : Author
Joellen Schildkraut
  • Function : Author
Jill S Barnholtz-Sloan
  • Function : Author
Sara H Olson
  • Function : Author
Jonine L Bernstein
  • Function : Author
Rose K Lai
  • Function : Author
Stephen Chanock
  • Function : Author
Preetha Rajaraman
  • Function : Author
Christoffer Johansen
  • Function : Author
Robert B Jenkins
  • Function : Author
Beatrice S Melin
  • Function : Author
Margaret R Wrensch
  • Function : Author
Melissa L Bondy
  • Function : Author

Abstract

Abstract 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 (OR SD = 3.91, P = 9.24 × 10 −3 ) and GBM (OR SD = 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 (OR SD = 1.11, P = 1.39 × 10 −2 and OR SD = 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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hal-04519628 , version 1 (25-03-2024)

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Charlie N Saunders, Alex J Cornish, Ben Kinnersley, Philip J Law, Richard S Houlston, et al.. Searching for causal relationships of glioma: a phenome-wide Mendelian randomisation study. British Journal of Cancer, 2020, 124 (2), pp.447-454. ⟨10.1038/s41416-020-01083-1⟩. ⟨hal-04519628⟩
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