Vitamin D levels and susceptibility to asthma, elevated immunoglobulin E levels, and atopic dermatitis: A Mendelian randomization study

Low circulating vitamin D levels have been associated with risk of asthma, atopic dermatitis, and elevated total immunoglobulin E (IgE). These epidemiological associations, if true, would have public health importance, since vitamin D insufficiency is common and correctable. We aimed to test whether...

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Published in:PLoS medicine Vol. 14; no. 5; p. e1002294
Main Authors: Manousaki, Despoina, Paternoster, Lavinia, Standl, Marie, Moffatt, Miriam F., Farrall, Martin, Bouzigon, Emmanuelle, Strachan, David P., Demenais, Florence, Lathrop, Mark, Cookson, William O. C. M., Richards, J. Brent
Format: Journal Article
Language:English
Published: United States Public Library of Science 09.05.2017
Public Library of Science (PLoS)
Subjects:
25-Hydroxyvitamin D
Adult
Asthma
Asthma - chemically induced
Asthma - epidemiology
Atopic dermatitis
Bias
Biology and Life Sciences
Causality
Causation
Child
Children
Consortia
Dermatitis
Dermatitis, Atopic - chemically induced
Dermatitis, Atopic - epidemiology
Disease
Eczema
Epidemiology
Genome-Wide Association Study
Genomes
Health aspects
Humans
Immunoglobulin E
Immunoglobulin E - blood
Immunoglobulins
Medical research
Medicine
Medicine and Health Sciences
Mendelian Randomization Analysis
Meta-analysis
Metabolism
Pediatrics
Physical sciences
Pleiotropy
Polymorphism, Single Nucleotide
Prevention
Public health
Randomization
Research and Analysis Methods
Retrospective Studies
Risk Factors
Sensitivity
Single-nucleotide polymorphism
Skin diseases
Social Sciences
Standard deviation
Studies
Sunlight
Test procedures
Vitamin D
Vitamin D - analogs & derivatives
Vitamin D - blood
ISSN:1549-1676, 1549-1277, 1549-1676
Online Access:Get full text
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Summary:Low circulating vitamin D levels have been associated with risk of asthma, atopic dermatitis, and elevated total immunoglobulin E (IgE). These epidemiological associations, if true, would have public health importance, since vitamin D insufficiency is common and correctable. We aimed to test whether genetically lowered vitamin D levels were associated with risk of asthma, atopic dermatitis, or elevated serum IgE levels, using Mendelian randomization (MR) methodology to control bias owing to confounding and reverse causation. The study employed data from the UK Biobank resource and from the SUNLIGHT, GABRIEL and EAGLE eczema consortia. Using four single-nucleotide polymorphisms (SNPs) strongly associated with 25-hydroxyvitamin D (25OHD) levels in 33,996 individuals, we conducted MR studies to estimate the effect of lowered 25OHD on the risk of asthma (n = 146,761), childhood onset asthma (n = 15,008), atopic dermatitis (n = 40,835), and elevated IgE level (n = 12,853) and tested MR assumptions in sensitivity analyses. None of the four 25OHD-lowering alleles were associated with asthma, atopic dermatitis, or elevated IgE levels (p ≥ 0.2). The MR odds ratio per standard deviation decrease in log-transformed 25OHD was 1.03 (95% confidence interval [CI] 0.90-1.19, p = 0.63) for asthma, 0.95 (95% CI 0.69-1.31, p = 0.76) for childhood-onset asthma, and 1.12 (95% CI 0.92-1.37, p = 0.27) for atopic dermatitis, and the effect size on log-transformed IgE levels was -0.40 (95% CI -1.65 to 0.85, p = 0.54). These results persisted in sensitivity analyses assessing population stratification and pleiotropy and vitamin D synthesis and metabolism pathways. The main limitations of this study are that the findings do not exclude an association between the studied outcomes and 1,25-dihydoxyvitamin D, the active form of vitamin D, the study was underpowered to detect effects smaller than an OR of 1.33 for childhood asthma, and the analyses were restricted to white populations of European ancestry. This research has been conducted using the UK Biobank Resource and data from the SUNLIGHT, GABRIEL and EAGLE Eczema consortia. In this study, we found no evidence that genetically determined reduction in 25OHD levels conferred an increased risk of asthma, atopic dermatitis, or elevated total serum IgE, suggesting that efforts to increase vitamin D are unlikely to reduce risks of atopic disease.
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Conceptualization: JBR WOCMC DM.Data curation: JBR DM LP MS MFM MF DPS EB ML FD.Formal analysis: JBR DM.Funding acquisition: JBR.Investigation: JBR DM.Project administration: JBR.Software: JBR DM.Supervision: JBR.Visualization: JBR DM.Writing – original draft: DM JBR.Writing – review & editing: MFM FD EB LP MS WOCMC MF DPS ML.
The authors have declared that no competing interests exist.
ISSN:1549-1676
1549-1277
1549-1676
DOI:10.1371/journal.pmed.1002294