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Associations of genetic determinants of serum vitamin B12 and folate concentrations with hay fever and asthma: a Mendelian randomization meta-analysis

European Journal of Clinical Nutrition volume 72, pages 264–271 (2018)Cite this article

Subjects

Abstract

Background/objectives

Studies of the effect of vitamin B12 and folate on the risk of asthma and hay fever have shown inconsistent results that may be biased by reverse causation and confounding. We used a Mendelian randomization approach to examine a potential causal effect of vitamin B12 and folate on hay fever, asthma, and selected biomarkers of allergy by using 11 vitamin B12-associated single-nucleotide polymorphisms (SNPs) and 2 folate-associated SNPs as unconfounded markers.

Subjects/methods

We included 162,736 participants from 9 population-based studies including the UK Biobank. Results were combined in instrumental variable and meta-analyses and effects expressed as odds ratios (ORs) or estimates with 95% confidence interval (CI).

Results

Using genetic proxies for B12 and folate, instrumental variable analyses did not show evidence for associations between serum B12 and hay fever: OR = 1.02 (95% CI: 0.98, 1.05), asthma: OR = 0.99 (95% CI: 0.95, 1.04), allergic sensitization: OR = 1.02 (95% CI: 0.74, 1.40), or change in serum IgE: 10.0% (95% CI: −9.6%, 29.6%) per 100 pg/ml B12. Similarly, there was no evidence for association between serum folate and hay fever: OR = 0.74 (95% CI: 0.45, 1.21), asthma: OR = 0.80 (95% CI: 0.43, 1.49), or allergic sensitization: OR = 1.92 (95% CI: 0.11, 33.45), but there was a statistically significant association with change in serum IgE: 2.0% (95% CI: 0.43%, 3.58%) per 0.1 ng/ml serum folate.

Conclusions

Our results did not support the hypothesis that levels of vitamin B12 and folate are causally related to hay fever, asthma, or biomarkers of allergy, but we found evidence of a positive association between serum folate and serum total IgE.

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Acknowledgements

Tea Skaaby was supported by the Lundbeck Foundation (Grant number R219-2016-471 and R165-2013-15410), the A.P. Møller Foundation for the Advancement of Medical Science (Grant number 15-363), the Harboe Foundation (Grant number 16152), Aase and Einar Danielsen’s Foundation (Grant number 10-001490), and the Weimann’s grant. The research has been conducted using the UK Biobank Resource (Application number: 17765). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen that was partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk).

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Authors and Affiliations

  1. Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark

    Tea Skaaby, Rikke K. Jacobsen, Line T. Møllehave, Nele Friedrich, Betina H. Thuesen, Daniel Mønsted Shabanzadeh, Torben Jørgensen & Allan Linneberg

  2. MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK

    Amy E. Taylor, Lavinia Paternoster & Marcus Munafò

  3. UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol, UK

    Amy E. Taylor & Marcus Munafò

  4. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany

    Nele Friedrich & Matthias Nauck

  5. Bispebjerg University Hospital, Digestive Disease Center, Bispebjerg Bakke 23, DK-2400, Copenhagen, Denmark

    Daniel Mønsted Shabanzadeh

  6. Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany

    Uwe Völker

  7. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany

    Henry Völzke

  8. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Torben Hansen, Oluf Pedersen & Niels Grarup

  9. Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Torben Jørgensen

  10. Faculty of Medicine, Aalborg University, Aalborg, Denmark

    Torben Jørgensen

  11. Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark

    Allan Linneberg

  12. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Allan Linneberg

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  1. Tea Skaaby
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Correspondence to Tea Skaaby.

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Skaaby, T., Taylor, A.E., Jacobsen, R.K. et al. Associations of genetic determinants of serum vitamin B12 and folate concentrations with hay fever and asthma: a Mendelian randomization meta-analysis. Eur J Clin Nutr 72, 264–271 (2018). https://doi.org/10.1038/s41430-017-0037-2

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