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
Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montréal, Canada.
MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom.
PLoS Med. 2017 May 9;14(5):e1002294. doi: 10.1371/journal.pmed.1002294. eCollection 2017 May.
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.
循环维生素D水平低与哮喘、特应性皮炎风险以及总免疫球蛋白E（IgE）升高有关。如果这些流行病学关联属实，将具有公共卫生重要性，因为维生素D不足很常见且可纠正。
我们旨在利用孟德尔随机化（MR）方法来控制混杂因素和反向因果关系导致的偏差，以检验基因决定的低维生素D水平是否与哮喘、特应性皮炎风险或血清IgE水平升高有关。该研究采用了英国生物银行资源以及SUNLIGHT、GABRIEL和EAGLE湿疹研究联盟的数据。我们在33996名个体中使用与25-羟基维生素D（25OHD）水平密切相关的四个单核苷酸多态性（SNP）进行了MR研究，以估计降低的25OHD对哮喘（n = 146761）、儿童期哮喘（n = 15008）、特应性皮炎（n = 40835）和IgE水平升高（n = 12853）风险的影响，并在敏感性分析中检验了MR假设。四个降低25OHD的等位基因均与哮喘、特应性皮炎或IgE水平升高无关（p≥0.2）。对于哮喘，经对数转换的25OHD每降低一个标准差时，MR比值比为1.03（95%置信区间[CI]0.90 - 1.19，p = 0.63）；对于儿童期哮喘，为0.95（95%CI 0.69 - 1.31，p = 0.76）；对于特应性皮炎，为1.12（95%CI 0.92 - 1.37，p = 0.27），对经对数转换的IgE水平的效应大小为 - 0.40（95%CI -
