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Use of Mendelian Randomization for Identifying Risk Factors for Brain Tumors

Research output: Contribution to journalArticle

Original languageEnglish
Article number525
Number of pages13
JournalFrontiers in Genetics
Volume9
DOIs
DateAccepted/In press - 19 Oct 2018
DatePublished (current) - 12 Nov 2018

Abstract

Gliomas are a group of primary brain tumors, the most common and aggressive subtype of which is glioblastoma. Glioblastoma has a median survival of just 15 months after diagnosis. Only previous exposure to ionizing radiation and particular inherited genetic syndromes are accepted risk factors for glioma; the vast majority of cases are thought to occur spontaneously. Previous observational studies have described associations between several risk factors and glioma, but studies are often conflicting and whether these associations reflect true casual relationships is unclear because observational studies may be susceptible to confounding, measurement error and reverse causation. Mendelian randomization (MR) is a form of instrumental variable analysis that can be used to provide supporting evidence for causal relationships between exposures (e.g., risk factors) and outcomes (e.g., disease onset). MR utilizes genetic variants, such as single nucleotide polymorphisms (SNPs), that are robustly associated with an exposure to determine whether there is a causal effect of the exposure on the outcome. MR is less susceptible to confounding, reverse causation and measurement errors as it is based on the random inheritance during conception of genetic variants that can be relatively accurately measured. In previous studies, MR has implicated a genetically predicted increase in telomere length with an increased risk of glioma, and found little evidence that obesity related factors, vitamin D or atopy are causal in glioma risk. In this review, we describe MR and its potential use to discover and validate novel risk factors, mechanistic factors, and therapeutic targets in glioma.

    Structured keywords

  • ICEP

    Research areas

  • Mendelian randomization, glioma, risk factors, genetic variant, causal inference, SNP, causal association

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Frontiers at https://www.frontiersin.org/articles/10.3389/fgene.2018.00525/full . Please refer to any applicable terms of use of the publisher.

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