Impact of atopy on risk of glioma: a Mendelian randomisation study

Disney-Hogg, Linden; Cornish, Alex J.; Sud, Amit; Law, Philip; Kinnersley, Ben; Jacobs, Daniel; Ostrom, Quinn T.; Labreche, Karim; Eckel‐Passow, Jeanette E.; Armstrong, Georgina; Claus, Elizabeth B.; Il’yasova, Dora; Schildkraut, Joellen M.; Barnholtz‐Sloan, Jill S.; Olson, Sara H.; Bernstein, Jonine L.; Lai, Rose; Schoemaker, Minouk J.; Simon, Matthias; Hoffmann, Per; Nöthen, Markus M.; Jöckel, Karl Heinz; Chanock, Stephen J.; Rajaraman, Preetha; Johansen, Christoffer; Jenkins, Robert B.; Melin, Beatrice; Wrensch, Margaret; Sanson, Marc; Bondy, Melissa L.; Houlston, Richard S.

doi:10.1186/s12916-018-1027-5

Cited by 44 publications

(40 citation statements)

References 46 publications

(64 reference statements)

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“…The authors found no significant association between glioma and asthma, hay fever, IgE levels, or self-reported allergy. For atopic dermatitis an inverse association was found (OR per 2.7-fold increase in odds of atopic dermatitis) by the IVW (OR 0.96, 95% CI 0.93–1.00, P = 0.041) and MLE methods (OR 0.96, 95% CI 0.94–0.99, P = 0.003), but not for weighted median estimate (WME) and mode-based estimate (MBE) methods ( Disney-Hogg et al, 2018a ), suggesting that having atopic dermatitis reduces the risk of glioma.…”

Section: Mr In Glioma Researchmentioning

confidence: 91%

“…Like most diseases, glioma GWAS to date have examined genetic variation in relation to the causes of disease risk, using case-control study designs, as opposed to disease progression ( Melin et al, 2017 ). The primary application of MR in glioma research has, therefore, focused primarily on causal effects of environmental exposures on disease risk ( Walsh et al, 2015 ; Haycock et al, 2017 ; Disney-Hogg et al, 2018a ; Takahashi et al, 2018 ), as opposed to survival. There are some instances where factors are involved in both disease incidence and progression, such as low-density lipoprotein cholesterol levels for heart disease risk and recurrence ( Ference et al, 2017 ), although such instances may be exceptional.…”

Section: Observational Epidemiological Studies Vs Mendelian Randomismentioning

confidence: 99%

“… Disney-Hogg et al (2018a) used an MR approach to evaluate the observed inverse relationship between allergies and glioma risk. The instrumental variables were SNPs robustly associated with atopic dermatitis, asthma and hay fever, IgE levels, and self-reported allergy.…”

Section: Mr In Glioma Researchmentioning

confidence: 99%

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Use of Mendelian Randomization for Identifying Risk Factors for Brain Tumors

et al. 2018

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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.

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Section: Mr In Glioma Researchmentioning

confidence: 91%

Section: Observational Epidemiological Studies Vs Mendelian Randomismentioning

confidence: 99%

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Use of Mendelian Randomization for Identifying Risk Factors for Brain Tumors

et al. 2018

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“…Indeed, Mendelian randomization has become a potent and effective statistical method for causal inference in observational studies, owing to recent achievements of genome-wide association studies (GWASs) [14][15][16][17][18][19][20][21][22]. In the present study, we employed single nucleotide polymorphisms (SNPs) associated with lipid traits as instrumental variables to determine their causal associations with gout.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the causal effects of blood lipid levels on gout with summary level GWAS data: two-sample Mendelian randomization and mediation analysis

Wang

Huang

et al. 2020

Preprint

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Background: Observational studies have identified gout patients are often comorbid with dyslipidemia, which is characterized by a decrease in high-density lipoprotein cholesterol (HDL) and an increase in triglycerides (TG). However, the relationship between dyslipidemia and gout is still unclear.Methods: We first performed Mendelian randomization (MR) to evaluate the causal effect of four lipid traits on gout and serum urate based on publicly available GWAS summary statistics ( n ~100,000 for lipid, 69,374 for gout and 110,347 for serum urate). We then employed multivariable MR to estimate the independent causal effect for lipid on gout via serum urate with mediation analysis.Results: MR showed each standard deviation (SD) (~12.26 mg/dL) increase in HDL resulted in about 25% (95% CI 9.0% ~ 38%, p = 3.31E-3) reduction of gout risk, with 0.09 mg/dL (95% CI: -0.12 -0.05, p = 7.00E-04) decrease in serum urate, and each SD (~112.33 mg/dL) increase of TG was associated with 0.10 mg/dL (95% CI: 0.06 ~ 0.14, p = 9.87E-05) increase in serum urate. Those results were robust against various sensitive analyses. Additionally, independent effects of HDL and TG on gout/serum urate were confirmed. Finally, mediation analysis demonstrated HDL or TG could also indirectly affect gout via the pathway of serum urate.Conclusion: Our study confirmed the causal associations between HDL (and TG) and gout, and further revealed the effect of HDL or TG on gout could also be mediated via serum urate.

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“…We have recently used MR to examine possible links between glioma with 25-hydroxyvitamin D levels, a common proxy for vitamin D levels, obesity, and atopy-related traits. [18][19][20] Here we have extended our analysis to examine the relationship of 37 potentially modifiable factors with glioma risk, using a two-sample MR framework. Genetic variants associated with these 37 factors were identified from the largest genome-wide association study (GWAS) conducted to date or meta-analysis of each trait.…”

mentioning

confidence: 99%

Lack of association between modifiable exposures and glioma risk: A Mendelian randomisation analysis

et al. 2019

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Background The etiological basis of glioma is poorly understood. We have used genetic markers in a Mendelian Randomisation (MR) framework to examine if lifestyle, cardiometabolic and inflammatory factors influence the risk of glioma. This methodology reduces bias from confounding and is not affected by reverse causation. Methods We identified genetic instruments for 37 potentially modifiable risk factors and evaluated their association with glioma risk using data from a genome-wide association study of 12,488 glioma patients and 18,169 controls. We used the estimated odds ratio of glioma associated with each of the genetically defined traits to infer evidence for a causal relationship with the following exposures: lifestyle and dietary factors (height, plasma IGF-1, blood carnitine, blood methionine, blood selenium, blood zinc, circulating adiponectin, circulating carotenoids, iron status, serum calcium, vitamin [A1, B12, B6, E and 25-hydroxyvitamin D], fatty acids levels [mono-unsaturated, omega-3 and omega-6] and circulating fetuin-A); cardiometabolic factors (birth weight, HDL cholesterol, LDL cholesterol, total cholesterol, total triglycerides, basal metabolic rate, body fat percentage, body mass index, fasting glucose, fasting proinsulin, HbA1C levels, diastolic and systolic blood pressure, waist circumference, waist-to-hip ratio) were included; inflammatory factors (C-reactive protein (CRP), plasma IL-6 sRa and serum IgE). Results After correction for the testing of multiple potential risk factors and excluding associations driven by one single nucleotide polymorphism (SNP) no significant association with glioma risk was observed (i.e. PCorrected > 0.05). Conclusions This study did not provide evidence supporting any of the 37 factors examined as having a significant influence on glioma risk.

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Impact of atopy on risk of glioma: a Mendelian randomisation study

Cited by 44 publications

References 46 publications

Use of Mendelian Randomization for Identifying Risk Factors for Brain Tumors

Use of Mendelian Randomization for Identifying Risk Factors for Brain Tumors

Evaluation of the causal effects of blood lipid levels on gout with summary level GWAS data: two-sample Mendelian randomization and mediation analysis

Lack of association between modifiable exposures and glioma risk: A Mendelian randomisation analysis

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