PMID- 28486474 OWN - NLM STAT- MEDLINE DCOM- 20170620 LR - 20210109 IS - 1549-1676 (Electronic) IS - 1549-1277 (Print) IS - 1549-1277 (Linking) VI - 14 IP - 5 DP - 2017 May TI - Vitamin D levels and susceptibility to asthma, elevated immunoglobulin E levels, and atopic dermatitis: A Mendelian randomization study. PG - e1002294 LID - 10.1371/journal.pmed.1002294 [doi] LID - e1002294 AB - 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. FAU - Manousaki, Despoina AU - Manousaki D AD - Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada. FAU - Paternoster, Lavinia AU - Paternoster L AUID- ORCID: 0000-0003-2514-0889 AD - MRC Integrative Epidemiology Unit, School of Social & Community Medicine, University of Bristol, Bristol, United Kingdom. FAU - Standl, Marie AU - Standl M AUID- ORCID: 0000-0002-5345-2049 AD - Institute of Epidemiology I, Helmholtz Zentrum Munchen-German Research Center for Environmental Health, Neuherberg, Germany. FAU - Moffatt, Miriam F AU - Moffatt MF AUID- ORCID: 0000-0001-7623-5840 AD - National Heart and Lung Institute, Imperial College London, London, United Kingdom. FAU - Farrall, Martin AU - Farrall M AUID- ORCID: 0000-0003-4564-2165 AD - Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom. AD - Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom. FAU - Bouzigon, Emmanuelle AU - Bouzigon E AUID- ORCID: 0000-0001-5756-4286 AD - Genetic Variation and Human Diseases Unit, UMR-946, INSERM, Universite Paris Diderot, Universite Sorbonne Paris Cite, Paris, France. FAU - Strachan, David P AU - Strachan DP AUID- ORCID: 0000-0001-7854-1366 AD - Population Health Research Institute, St George's University of London, London, United Kingdom. FAU - Demenais, Florence AU - Demenais F AD - Genetic Variation and Human Diseases Unit, UMR-946, INSERM, Universite Paris Diderot, Universite Sorbonne Paris Cite, Paris, France. FAU - Lathrop, Mark AU - Lathrop M AD - McGill University and Genome Quebec Innovation Centre, Montreal, Canada. FAU - Cookson, William O C M AU - Cookson WOCM AD - National Heart and Lung Institute, Imperial College London, London, United Kingdom. AD - Royal Brompton and Harefield NHS Foundation Trust, London, United Kingdom. FAU - Richards, J Brent AU - Richards JB AUID- ORCID: 0000-0002-3746-9086 AD - Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Canada. AD - Departments of Medicine and Human Genetics, McGill University, Montreal, Canada. AD - Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom. LA - eng GR - G1000758/MRC_/Medical Research Council/United Kingdom GR - MC_QA137853/MRC_/Medical Research Council/United Kingdom GR - MR/J012165/1/MRC_/Medical Research Council/United Kingdom GR - RE/13/1/30181/BHF_/British Heart Foundation/United Kingdom GR - 090532/Z/09/Z/WT_/Wellcome Trust/United Kingdom GR - MC_PC_12028/MRC_/Medical Research Council/United Kingdom GR - MC_PC_17228/MRC_/Medical Research Council/United Kingdom GR - WT084703MA/WT_/Wellcome Trust/United Kingdom GR - MC_UU_12013/4/MRC_/Medical Research Council/United Kingdom GR - FRN 119 462/Canadian Institute of Health Research/International PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20170509 PL - United States TA - PLoS Med JT - PLoS medicine JID - 101231360 RN - 1406-16-2 (Vitamin D) RN - 37341-29-0 (Immunoglobulin E) RN - A288AR3C9H (25-hydroxyvitamin D) SB - IM MH - Adult MH - Asthma/chemically induced/*epidemiology MH - Child MH - Dermatitis, Atopic/chemically induced/*epidemiology MH - Genome-Wide Association Study MH - Humans MH - Immunoglobulin E/*blood MH - *Mendelian Randomization Analysis MH - *Polymorphism, Single Nucleotide MH - Retrospective Studies MH - Risk Factors MH - Vitamin D/*analogs & derivatives/blood PMC - PMC5423551 COIS- The authors have declared that no competing interests exist. EDAT- 2017/05/10 06:00 MHDA- 2017/06/21 06:00 PMCR- 2017/05/09 CRDT- 2017/05/10 06:00 PHST- 2016/12/30 00:00 [received] PHST- 2017/03/27 00:00 [accepted] PHST- 2017/05/10 06:00 [entrez] PHST- 2017/05/10 06:00 [pubmed] PHST- 2017/06/21 06:00 [medline] PHST- 2017/05/09 00:00 [pmc-release] AID - PMEDICINE-D-16-04194 [pii] AID - 10.1371/journal.pmed.1002294 [doi] PST - epublish SO - PLoS Med. 2017 May 9;14(5):e1002294. doi: 10.1371/journal.pmed.1002294. eCollection 2017 May.