TY - JOUR
T1 - Impact of atopy on risk of glioma
T2 - a Mendelian randomisation study
AU - Disney-Hogg, Linden
AU - Cornish, Alex J
AU - Sud, Amit
AU - Law, Philip J
AU - Kinnersley, Ben
AU - Jacobs, Daniel I
AU - Ostrom, Quinn T
AU - Labreche, Karim
AU - Eckel-Passow, Jeanette E
AU - Armstrong, Georgina N
AU - Claus, Elizabeth B
AU - Il'yasova, Dora
AU - Schildkraut, Joellen
AU - Barnholtz-Sloan, Jill S
AU - Olson, Sara H
AU - Bernstein, Jonine L
AU - Lai, Rose K
AU - Schoemaker, Minouk J
AU - Simon, Matthias
AU - Hoffmann, Per
AU - Nöthen, Markus M
AU - Jöckel, Karl-Heinz
AU - Chanock, Stephen
AU - Rajaraman, Preetha
AU - Johansen, Christoffer
AU - Jenkins, Robert B
AU - Melin, Beatrice S
AU - Wrensch, Margaret R
AU - Sanson, Marc
AU - Bondy, Melissa L
AU - Houlston, Richard S
PY - 2018
Y1 - 2018
N2 - BACKGROUND: An inverse relationship between allergies with glioma risk has been reported in several but not all epidemiological observational studies. We performed an analysis of genetic variants associated with atopy to assess the relationship with glioma risk using Mendelian randomisation (MR), an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.METHODS: Two-sample MR was undertaken using genome-wide association study data. We used single nucleotide polymorphisms (SNPs) associated with atopic dermatitis, asthma and hay fever, IgE levels, and self-reported allergy as instrumental variables. We calculated MR estimates for the odds ratio (OR) for each risk factor with glioma using SNP-glioma estimates from 12,488 cases and 18,169 controls, using inverse-variance weighting (IVW), maximum likelihood estimation (MLE), weighted median estimate (WME) and mode-based estimate (MBE) methods. Violation of MR assumptions due to directional pleiotropy were sought using MR-Egger regression and HEIDI-outlier analysis.RESULTS: Under IVW, MLE, WME and MBE methods, associations between glioma risk with asthma and hay fever, self-reported allergy and IgE levels were non-significant. An inverse relationship between atopic dermatitis and glioma risk was found by IVW (OR 0.96, 95% confidence interval (CI) 0.93-1.00, P = 0.041) and MLE (OR 0.96, 95% CI 0.94-0.99, P = 0.003), but not by WME (OR 0.96, 95% CI 0.91-1.01, P = 0.114) or MBE (OR 0.97, 95% CI 0.92-1.02, P = 0.194).CONCLUSIONS: Our investigation does not provide strong evidence for relationship between atopy and the risk of developing glioma, but findings do not preclude a small effect in relation to atopic dermatitis. Our analysis also serves to illustrate the value of using several MR methods to derive robust conclusions.
AB - BACKGROUND: An inverse relationship between allergies with glioma risk has been reported in several but not all epidemiological observational studies. We performed an analysis of genetic variants associated with atopy to assess the relationship with glioma risk using Mendelian randomisation (MR), an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.METHODS: Two-sample MR was undertaken using genome-wide association study data. We used single nucleotide polymorphisms (SNPs) associated with atopic dermatitis, asthma and hay fever, IgE levels, and self-reported allergy as instrumental variables. We calculated MR estimates for the odds ratio (OR) for each risk factor with glioma using SNP-glioma estimates from 12,488 cases and 18,169 controls, using inverse-variance weighting (IVW), maximum likelihood estimation (MLE), weighted median estimate (WME) and mode-based estimate (MBE) methods. Violation of MR assumptions due to directional pleiotropy were sought using MR-Egger regression and HEIDI-outlier analysis.RESULTS: Under IVW, MLE, WME and MBE methods, associations between glioma risk with asthma and hay fever, self-reported allergy and IgE levels were non-significant. An inverse relationship between atopic dermatitis and glioma risk was found by IVW (OR 0.96, 95% confidence interval (CI) 0.93-1.00, P = 0.041) and MLE (OR 0.96, 95% CI 0.94-0.99, P = 0.003), but not by WME (OR 0.96, 95% CI 0.91-1.01, P = 0.114) or MBE (OR 0.97, 95% CI 0.92-1.02, P = 0.194).CONCLUSIONS: Our investigation does not provide strong evidence for relationship between atopy and the risk of developing glioma, but findings do not preclude a small effect in relation to atopic dermatitis. Our analysis also serves to illustrate the value of using several MR methods to derive robust conclusions.
KW - Genome-Wide Association Study/methods
KW - Genotype
KW - Glioma/etiology
KW - Humans
KW - Mendelian Randomization Analysis/methods
KW - Risk Factors
U2 - 10.1186/s12916-018-1027-5
DO - 10.1186/s12916-018-1027-5
M3 - Journal article
C2 - 29540232
VL - 16
SP - 1
EP - 13
JO - BMC Medicine
JF - BMC Medicine
SN - 1741-7015
IS - 1
M1 - 42
ER -