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PLoS Med. 2017 May 9;14(5):e1002294. doi: 10.1371/journal.pmed.1002294. eCollection 2017 May.

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

Author information

1
Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montréal, Canada.
2
MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom.
3
Institute of Epidemiology I, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
4
National Heart and Lung Institute, Imperial College London, London, United Kingdom.
5
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
6
Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
7
Genetic Variation and Human Diseases Unit, UMR-946, INSERM, Université Paris Diderot, Université Sorbonne Paris Cité, Paris, France.
8
Population Health Research Institute, St George's University of London, London, United Kingdom.
9
McGill University and Genome Québec Innovation Centre, Montréal, Canada.
10
Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom.
11
Departments of Medicine and Human Genetics, McGill University, Montréal, Canada.
12
Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom.

Abstract

BACKGROUND:

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.

METHODS AND FINDINGS:

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.

CONCLUSIONS:

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.

PMID:
28486474
PMCID:
PMC5423551
DOI:
10.1371/journal.pmed.1002294
[Indexed for MEDLINE]
Free PMC Article

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