Mendelian randomisation study of the relationship between vitamin D and risk of glioma

Hannah Takahashi; Alex J Cornish; Amit Sud; Philip J Law; Ben Kinnersley; Quinn T Ostrom; Karim Labreche; Jeanette E Eckel-Passow; Georgina N Armstrong; Elizabeth B Claus; Dora Ll'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; Clare Turnbull; Richard S Houlston

doi:10.1038/s41598-018-20844-w

Mendelian randomisation study of the relationship between vitamin D and risk of glioma

Hannah Takahashi, Alex J Cornish, Amit Sud, Philip J Law, Ben Kinnersley, Quinn T Ostrom, Karim Labreche, Jeanette E Eckel-Passow, Georgina N Armstrong, Elizabeth B Claus, Dora Ll'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 NöthenKarl-Heinz Jöckel, Stephen Chanock, Preetha Rajaraman, Christoffer Johansen, Robert B Jenkins, Beatrice S Melin, Margaret R Wrensch, Marc Sanson, Melissa L Bondy, Clare Turnbull, Richard S Houlston

Department of Clinical Medicine

9 Citations (Scopus)

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Abstract

To examine for a causal relationship between vitamin D and glioma risk we performed an analysis of genetic variants associated with serum 25-hydroxyvitamin D (25(OH)D) levels using Mendelian randomisation (MR), an approach unaffected by biases from confounding. Two-sample MR was undertaken using genome-wide association study data. Single nucleotide polymorphisms (SNPs) associated with 25(OH)D levels were used as instrumental variables (IVs). We calculated MR estimates for the odds ratio (OR) for 25(OH)D levels with glioma using SNP-glioma estimates from 12,488 cases and 18,169 controls, using inverse-variance weighted (IVW) and maximum likelihood estimation (MLE) methods. A non-significant association between 25(OH)D levels and glioma risk was shown using both the IVW (OR = 1.21, 95% confidence interval [CI] = 0.90-1.62, P = 0.201) and MLE (OR = 1.20, 95% CI = 0.98-1.48, P = 0.083) methods. In an exploratory analysis of tumour subtype, an inverse relationship between 25(OH)D levels and glioblastoma (GBM) risk was identified using the MLE method (OR = 0.62, 95% CI = 0.43-0.89, P = 0.010), but not the IVW method (OR = 0.62, 95% CI = 0.37-1.04, P = 0.070). No statistically significant association was shown between 25(OH)D levels and non-GBM glioma. Our results do not provide evidence for a causal relationship between 25(OH)D levels and all forms of glioma risk. More evidence is required to explore the relationship between 25(OH)D levels and risk of GBM.

Original language	English
Article number	2339
Journal	Scientific Reports
Volume	8
Number of pages	8
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-018-20844-w
Publication status	Published - 1 Dec 2018

Keywords

Brain Neoplasms/blood
Genetic Predisposition to Disease
Genetic Variation
Glioma/blood
Humans
Mendelian Randomization Analysis
Polymorphism, Single Nucleotide
Vitamin D/blood

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Takahashi, H., Cornish, A. J., Sud, A., Law, P. J., Kinnersley, B., Ostrom, Q. T., Labreche, K., Eckel-Passow, J. E., Armstrong, G. N., Claus, E. B., Ll'yasova, D., Schildkraut, J., Barnholtz-Sloan, J. S., Olson, S. H., Bernstein, J. L., Lai, R. K., Schoemaker, M. J., Simon, M., Hoffmann, P., ... Houlston, R. S. (2018). Mendelian randomisation study of the relationship between vitamin D and risk of glioma. Scientific Reports, 8, [2339]. https://doi.org/10.1038/s41598-018-20844-w

Takahashi, H, Cornish, AJ, Sud, A, Law, PJ, Kinnersley, B, Ostrom, QT, Labreche, K, Eckel-Passow, JE, Armstrong, GN, Claus, EB, Ll'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, Turnbull, C & Houlston, RS 2018, 'Mendelian randomisation study of the relationship between vitamin D and risk of glioma', Scientific Reports, vol. 8, 2339. https://doi.org/10.1038/s41598-018-20844-w

@article{d029d391f6724c3fb9747036c7666235,

title = "Mendelian randomisation study of the relationship between vitamin D and risk of glioma",

abstract = "To examine for a causal relationship between vitamin D and glioma risk we performed an analysis of genetic variants associated with serum 25-hydroxyvitamin D (25(OH)D) levels using Mendelian randomisation (MR), an approach unaffected by biases from confounding. Two-sample MR was undertaken using genome-wide association study data. Single nucleotide polymorphisms (SNPs) associated with 25(OH)D levels were used as instrumental variables (IVs). We calculated MR estimates for the odds ratio (OR) for 25(OH)D levels with glioma using SNP-glioma estimates from 12,488 cases and 18,169 controls, using inverse-variance weighted (IVW) and maximum likelihood estimation (MLE) methods. A non-significant association between 25(OH)D levels and glioma risk was shown using both the IVW (OR = 1.21, 95% confidence interval [CI] = 0.90-1.62, P = 0.201) and MLE (OR = 1.20, 95% CI = 0.98-1.48, P = 0.083) methods. In an exploratory analysis of tumour subtype, an inverse relationship between 25(OH)D levels and glioblastoma (GBM) risk was identified using the MLE method (OR = 0.62, 95% CI = 0.43-0.89, P = 0.010), but not the IVW method (OR = 0.62, 95% CI = 0.37-1.04, P = 0.070). No statistically significant association was shown between 25(OH)D levels and non-GBM glioma. Our results do not provide evidence for a causal relationship between 25(OH)D levels and all forms of glioma risk. More evidence is required to explore the relationship between 25(OH)D levels and risk of GBM.",

keywords = "Brain Neoplasms/blood, Genetic Predisposition to Disease, Genetic Variation, Glioma/blood, Humans, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Vitamin D/blood",

author = "Hannah Takahashi and Cornish, {Alex J} and Amit Sud and Law, {Philip J} and Ben Kinnersley and Ostrom, {Quinn T} and Karim Labreche and Eckel-Passow, {Jeanette E} and Armstrong, {Georgina N} and Claus, {Elizabeth B} and Dora Ll'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 Clare Turnbull and Houlston, {Richard S}",

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doi = "10.1038/s41598-018-20844-w",

language = "English",

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journal = "Scientific Reports",

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T1 - Mendelian randomisation study of the relationship between vitamin D and risk of glioma

AU - Takahashi, Hannah

AU - Cornish, Alex J

AU - Sud, Amit

AU - Law, Philip J

AU - Kinnersley, Ben

AU - Ostrom, Quinn T

AU - Labreche, Karim

AU - Eckel-Passow, Jeanette E

AU - Armstrong, Georgina N

AU - Claus, Elizabeth B

AU - Ll'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 - Turnbull, Clare

AU - Houlston, Richard S

PY - 2018/12/1

Y1 - 2018/12/1

N2 - To examine for a causal relationship between vitamin D and glioma risk we performed an analysis of genetic variants associated with serum 25-hydroxyvitamin D (25(OH)D) levels using Mendelian randomisation (MR), an approach unaffected by biases from confounding. Two-sample MR was undertaken using genome-wide association study data. Single nucleotide polymorphisms (SNPs) associated with 25(OH)D levels were used as instrumental variables (IVs). We calculated MR estimates for the odds ratio (OR) for 25(OH)D levels with glioma using SNP-glioma estimates from 12,488 cases and 18,169 controls, using inverse-variance weighted (IVW) and maximum likelihood estimation (MLE) methods. A non-significant association between 25(OH)D levels and glioma risk was shown using both the IVW (OR = 1.21, 95% confidence interval [CI] = 0.90-1.62, P = 0.201) and MLE (OR = 1.20, 95% CI = 0.98-1.48, P = 0.083) methods. In an exploratory analysis of tumour subtype, an inverse relationship between 25(OH)D levels and glioblastoma (GBM) risk was identified using the MLE method (OR = 0.62, 95% CI = 0.43-0.89, P = 0.010), but not the IVW method (OR = 0.62, 95% CI = 0.37-1.04, P = 0.070). No statistically significant association was shown between 25(OH)D levels and non-GBM glioma. Our results do not provide evidence for a causal relationship between 25(OH)D levels and all forms of glioma risk. More evidence is required to explore the relationship between 25(OH)D levels and risk of GBM.

AB - To examine for a causal relationship between vitamin D and glioma risk we performed an analysis of genetic variants associated with serum 25-hydroxyvitamin D (25(OH)D) levels using Mendelian randomisation (MR), an approach unaffected by biases from confounding. Two-sample MR was undertaken using genome-wide association study data. Single nucleotide polymorphisms (SNPs) associated with 25(OH)D levels were used as instrumental variables (IVs). We calculated MR estimates for the odds ratio (OR) for 25(OH)D levels with glioma using SNP-glioma estimates from 12,488 cases and 18,169 controls, using inverse-variance weighted (IVW) and maximum likelihood estimation (MLE) methods. A non-significant association between 25(OH)D levels and glioma risk was shown using both the IVW (OR = 1.21, 95% confidence interval [CI] = 0.90-1.62, P = 0.201) and MLE (OR = 1.20, 95% CI = 0.98-1.48, P = 0.083) methods. In an exploratory analysis of tumour subtype, an inverse relationship between 25(OH)D levels and glioblastoma (GBM) risk was identified using the MLE method (OR = 0.62, 95% CI = 0.43-0.89, P = 0.010), but not the IVW method (OR = 0.62, 95% CI = 0.37-1.04, P = 0.070). No statistically significant association was shown between 25(OH)D levels and non-GBM glioma. Our results do not provide evidence for a causal relationship between 25(OH)D levels and all forms of glioma risk. More evidence is required to explore the relationship between 25(OH)D levels and risk of GBM.

KW - Brain Neoplasms/blood

KW - Genetic Predisposition to Disease

KW - Genetic Variation

KW - Glioma/blood

KW - Humans

KW - Mendelian Randomization Analysis

KW - Polymorphism, Single Nucleotide

KW - Vitamin D/blood

U2 - 10.1038/s41598-018-20844-w

DO - 10.1038/s41598-018-20844-w

M3 - Journal article

C2 - 29402980

SN - 2045-2322

VL - 8

JO - Scientific Reports

JF - Scientific Reports

M1 - 2339

ER -

Mendelian randomisation study of the relationship between vitamin D and risk of glioma

Abstract

Keywords

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