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 & 11 others Karl Heinz Jöckel, Stephen Chanock, Preetha Rajaraman, Christoffer Johansen, Robert Brian Jenkins, Beatrice S. Melin, Margaret R. Wrensch, Marc Sanson, Melissa L. Bondy, Clare Turnbull, Richard S. Houlston

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 languageEnglish (US)
Article number2339
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Random Allocation
Vitamin D
Glioma
Odds Ratio
Confidence Intervals
Glioblastoma
Single Nucleotide Polymorphism
Genome-Wide Association Study
Serum
Neoplasms

ASJC Scopus subject areas

  • General

Cite this

Takahashi, H., Cornish, A. J., Sud, A., Law, P. J., Kinnersley, B., Ostrom, Q. T., ... Houlston, R. S. (2018). Mendelian randomisation study of the relationship between Vitamin D and risk of glioma. Scientific Reports, 8(1), [2339]. https://doi.org/10.1038/s41598-018-20844-w

Mendelian randomisation study of the relationship between Vitamin D and risk of glioma. / Takahashi, Hannah; Cornish, Alex J.; Sud, Amit; Law, Philip J.; Kinnersley, Ben; Ostrom, Quinn T.; Labreche, Karim; Eckel-Passow, Jeanette E; Armstrong, Georgina N.; Claus, Elizabeth B.; Ll'Yasova, Dora; Schildkraut, Joellen; Barnholtz-Sloan, Jill S.; Olson, Sara H.; Bernstein, Jonine L.; Lai, Rose K.; Schoemaker, Minouk J.; Simon, Matthias; Hoffmann, Per; Nöthen, Markus M.; Jöckel, Karl Heinz; Chanock, Stephen; Rajaraman, Preetha; Johansen, Christoffer; Jenkins, Robert Brian; Melin, Beatrice S.; Wrensch, Margaret R.; Sanson, Marc; Bondy, Melissa L.; Turnbull, Clare; Houlston, Richard S.

In: Scientific Reports, Vol. 8, No. 1, 2339, 01.12.2018.

Research output: Contribution to journalArticle

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, KH, 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, no. 1, 2339. https://doi.org/10.1038/s41598-018-20844-w
Takahashi H, Cornish AJ, Sud A, Law PJ, Kinnersley B, Ostrom QT et al. Mendelian randomisation study of the relationship between Vitamin D and risk of glioma. Scientific Reports. 2018 Dec 1;8(1). 2339. https://doi.org/10.1038/s41598-018-20844-w
Takahashi, Hannah ; Cornish, Alex J. ; Sud, Amit ; Law, Philip J. ; Kinnersley, Ben ; Ostrom, Quinn T. ; Labreche, Karim ; Eckel-Passow, Jeanette E ; Armstrong, Georgina N. ; Claus, Elizabeth B. ; Ll'Yasova, Dora ; Schildkraut, Joellen ; Barnholtz-Sloan, Jill S. ; Olson, Sara H. ; Bernstein, Jonine L. ; Lai, Rose K. ; Schoemaker, Minouk J. ; Simon, Matthias ; Hoffmann, Per ; Nöthen, Markus M. ; Jöckel, Karl Heinz ; Chanock, Stephen ; Rajaraman, Preetha ; Johansen, Christoffer ; Jenkins, Robert Brian ; Melin, Beatrice S. ; Wrensch, Margaret R. ; Sanson, Marc ; Bondy, Melissa L. ; Turnbull, Clare ; Houlston, Richard S. / Mendelian randomisation study of the relationship between Vitamin D and risk of glioma. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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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.",
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