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

摘要

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.