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

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

doi:10.1186/s12916-018-1027-5

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

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

Department of Clinical Medicine

13 Citations (Scopus)

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Abstract

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.

Original language	English
Article number	42
Journal	BMC Medicine
Volume	16
Issue number	1
Pages (from-to)	1-13
Number of pages	13
ISSN	1741-7015
DOIs	https://doi.org/10.1186/s12916-018-1027-5
Publication status	Published - 15 Mar 2018

Keywords

Genome-Wide Association Study/methods
Genotype
Glioma/etiology
Humans
Mendelian Randomization Analysis/methods
Risk Factors

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Disney-Hogg, L., Cornish, A. J., Sud, A., Law, P. J., Kinnersley, B., Jacobs, D. I., Ostrom, Q. T., Labreche, K., Eckel-Passow, J. E., Armstrong, G. N., Claus, E. B., Il'yasova, D., Schildkraut, J., Barnholtz-Sloan, J. S., Olson, S. H., Bernstein, J. L., Lai, R. K., Schoemaker, M. J., Simon, M., ... Houlston, R. S. (2018). Impact of atopy on risk of glioma: a Mendelian randomisation study. BMC Medicine, 16(1), 1-13. Article 42. https://doi.org/10.1186/s12916-018-1027-5

Disney-Hogg, L, Cornish, AJ, Sud, A, Law, PJ, Kinnersley, B, Jacobs, DI, Ostrom, QT, Labreche, K, Eckel-Passow, JE, Armstrong, GN, Claus, EB, Il'yasova, D, Schildkraut, J, Barnholtz-Sloan, JS, Olson, SH, Bernstein, JL, Lai, RK, Schoemaker, MJ, Simon, M, Hoffmann, P, Nöthen, MM, Jöckel, K-H, Chanock, S, Rajaraman, P, Johansen, C, Jenkins, RB, Melin, BS, Wrensch, MR, Sanson, M, Bondy, ML & Houlston, RS 2018, 'Impact of atopy on risk of glioma: a Mendelian randomisation study', BMC Medicine, vol. 16, no. 1, 42, pp. 1-13. https://doi.org/10.1186/s12916-018-1027-5

@article{c93ca7d4fb4d456e8becb92b1968b24a,

title = "Impact of atopy on risk of glioma: a Mendelian randomisation study",

abstract = "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.",

keywords = "Genome-Wide Association Study/methods, Genotype, Glioma/etiology, Humans, Mendelian Randomization Analysis/methods, Risk Factors",

author = "Linden Disney-Hogg and Cornish, {Alex J} and Amit Sud and Law, {Philip J} and Ben Kinnersley and Jacobs, {Daniel I} and Ostrom, {Quinn T} and Karim Labreche and Eckel-Passow, {Jeanette E} and Armstrong, {Georgina N} and Claus, {Elizabeth B} and Dora Il'yasova and Joellen Schildkraut and Barnholtz-Sloan, {Jill S} and Olson, {Sara H} and Bernstein, {Jonine L} and Lai, {Rose K} and Schoemaker, {Minouk J} and Matthias Simon and Per Hoffmann and N{\"o}then, {Markus M} and Karl-Heinz J{\"o}ckel and Stephen Chanock and Preetha Rajaraman and Christoffer Johansen and Jenkins, {Robert B} and Melin, {Beatrice S} and Wrensch, {Margaret R} and Marc Sanson and Bondy, {Melissa L} and Houlston, {Richard S}",

year = "2018",

month = mar,

day = "15",

doi = "10.1186/s12916-018-1027-5",

language = "English",

volume = "16",

pages = "1--13",

journal = "BMC Medicine",

issn = "1741-7015",

publisher = "BioMed Central Ltd.",

number = "1",

}

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 - 2018/3/15

Y1 - 2018/3/15

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

SN - 1741-7015

VL - 16

SP - 1

EP - 13

JO - BMC Medicine

JF - BMC Medicine

IS - 1

M1 - 42

ER -

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

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Keywords

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