Searching for causal relationships of glioma: A phenome-wide Mendelian randomisation study Journal Article
| Authors: | Saunders, C. N.; Cornish, A. J.; Kinnersley, B.; Law, P. J.; Houlston, R. S.; and Collaborators |
| Contributors: | Olson, S. H.; Bernstein, J. L. |
| Article Title: | Searching for causal relationships of glioma: A phenome-wide Mendelian randomisation study |
| 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 (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. © 2020, The Author(s). |
| Journal Title: | British Journal of Cancer |
| Volume: | 124 |
| Issue: | 2 |
| ISSN: | 0007-0920 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2021-01-19 |
| Start Page: | 447 |
| End Page: | 454 |
| Language: | English |
| DOI: | 10.1038/s41416-020-01083-1 |
| PUBMED: | 33020596 |
| PROVIDER: | scopus |
| PMCID: | PMC7852872 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2021 -- Source: Scopus |
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