Searching for causal relationships of glioma: a phenome-wide Mendelian randomisation study
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- Fulltext
Forlagets udgivne version, 766 KB, PDF-dokument
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.
Originalsprog | Engelsk |
---|---|
Tidsskrift | British Journal of Cancer |
Vol/bind | 124 |
Udgave nummer | 2 |
Sider (fra-til) | 447-454 |
Antal sider | 8 |
ISSN | 0007-0920 |
DOI | |
Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:
Funding information C.N.S. was supported by Cancer Research UK (C1298/A8362).
Publisher Copyright:
© 2020, The Author(s).
Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk
ID: 302051157