Tea Skaaby1, Amy E Taylor2,3, Rikke K Jacobsen4, Line T Møllehave4, Nele Friedrich4,5, Betina H Thuesen4, Daniel Mønsted Shabanzadeh4,6, Lavinia Paternoster2, Uwe Völker7, Matthias Nauck5, Henry Völzke8, Marcus Munafò2,3, Torben Hansen9, Oluf Pedersen9, Torben Jørgensen4,10,11, Niels Grarup9, Allan Linneberg4,12,13. 1. Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark. tea.skaaby.01@regionh.dk. 2. MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK. 3. UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol, UK. 4. Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark. 5. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany. 6. Bispebjerg University Hospital, Digestive Disease Center, Bispebjerg Bakke 23, DK-2400, Copenhagen, Denmark. 7. Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany. 8. Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany. 9. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section on Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 10. Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 11. Faculty of Medicine, Aalborg University, Aalborg, Denmark. 12. Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark. 13. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
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.
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.