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

Tea Skaaby; Amy E. Taylor; Rikke K. Jacobsen; Line T. Møllehave; Nele Friedrich; Betina H. Thuesen; Daniel Mønsted Shabanzadeh; Lavinia Paternoster; Uwe Völker; Matthias Nauck; Henry Völzke; Marcus Munafò; Torben Hansen; Oluf Pedersen; Torben Jørgensen; Niels Grarup; Allan Linneberg

doi:10.1038/s41430-017-0037-2

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

Tea Skaaby^*, Amy E. Taylor, Rikke K. Jacobsen, Line T. Møllehave, Nele Friedrich, Betina H. Thuesen, Daniel Mønsted Shabanzadeh, Lavinia Paternoster, Uwe Völker, Matthias Nauck, Henry Völzke, Marcus Munafò, Torben Hansen, Oluf Pedersen, Torben Jørgensen, Niels Grarup, Allan Linneberg

^*Corresponding author for this work

3 Citations (Scopus)

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.

Original language	English
Journal	European Journal of Clinical Nutrition
Volume	72
Issue number	2
Pages (from-to)	264–271
Number of pages	8
ISSN	0954-3007
DOIs	https://doi.org/10.1038/s41430-017-0037-2
Publication status	Published - 2018

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Skaaby, T., Taylor, A. E., Jacobsen, R. K., Møllehave, L. T., Friedrich, N., Thuesen, B. H., Shabanzadeh, D. M., Paternoster, L., Völker, U., Nauck, M., Völzke, H., Munafò, M., Hansen, T., Pedersen, O., Jørgensen, T., Grarup, N., & Linneberg, A. (2018). 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, 72(2), 264–271. https://doi.org/10.1038/s41430-017-0037-2

Associations of genetic determinants of serum vitamin B12 and folate concentrations with hay fever and asthma : a Mendelian randomization meta-analysis. / Skaaby, Tea; Taylor, Amy E.; Jacobsen, Rikke K. et al.

In: European Journal of Clinical Nutrition, Vol. 72, No. 2, 2018, p. 264–271.

Research output: Contribution to journal › Journal article › Research › peer-review

Skaaby, T, Taylor, AE, Jacobsen, RK, Møllehave, LT, Friedrich, N, Thuesen, BH, Shabanzadeh, DM, Paternoster, L, Völker, U, Nauck, M, Völzke, H, Munafò, M, Hansen, T , Pedersen, O, Jørgensen, T, Grarup, N & Linneberg, A 2018, '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, vol. 72, no. 2, pp. 264–271. https://doi.org/10.1038/s41430-017-0037-2

@article{6726a58d4893445f87bbb2e9bfca7d8a,

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

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.",

author = "Tea Skaaby and Taylor, {Amy E.} and Jacobsen, {Rikke K.} and M{\o}llehave, {Line T.} and Nele Friedrich and Thuesen, {Betina H.} and Shabanzadeh, {Daniel M{\o}nsted} and Lavinia Paternoster and Uwe V{\"o}lker and Matthias Nauck and Henry V{\"o}lzke and Marcus Munaf{\`o} and Torben Hansen and Oluf Pedersen and Torben J{\o}rgensen and Niels Grarup and Allan Linneberg",

year = "2018",

doi = "10.1038/s41430-017-0037-2",

language = "English",

volume = "72",

pages = "264–271",

journal = "European Journal of Clinical Nutrition",

issn = "0954-3007",

publisher = "nature publishing group",

number = "2",

}

TY - JOUR

T1 - Associations of genetic determinants of serum vitamin B12 and folate concentrations with hay fever and asthma

T2 - a Mendelian randomization meta-analysis

AU - Skaaby, Tea

AU - Taylor, Amy E.

AU - Jacobsen, Rikke K.

AU - Møllehave, Line T.

AU - Friedrich, Nele

AU - Thuesen, Betina H.

AU - Shabanzadeh, Daniel Mønsted

AU - Paternoster, Lavinia

AU - Völker, Uwe

AU - Nauck, Matthias

AU - Völzke, Henry

AU - Munafò, Marcus

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Jørgensen, Torben

AU - Grarup, Niels

AU - Linneberg, Allan

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1038/s41430-017-0037-2

DO - 10.1038/s41430-017-0037-2

M3 - Journal article

C2 - 29249824

AN - SCOPUS:85038071914

SN - 0954-3007

VL - 72

SP - 264

EP - 271

JO - European Journal of Clinical Nutrition

JF - European Journal of Clinical Nutrition

IS - 2

ER -

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

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