Dataset Information

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?-4) were observed between phenotypes and glioma under the IVW-RE model. Suggestive associations (1.58?×?10^-4?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.

SUBMITTER: Saunders CN

PROVIDER: S-EPMC7852872 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Saunders Charlie N CN Cornish Alex J AJ Kinnersley Ben B Law Philip J PJ Houlston Richard S RS

British journal of cancer 20201006 2

<h4>Background</h4>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.<h4>Methods</h4>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-weigh ...[more]

PMID: 33020596

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Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

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