Dataset Information

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

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.

SUBMITTER: Manousaki D

PROVIDER: S-EPMC5423551 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Publications

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

Manousaki Despoina D Paternoster Lavinia L Standl Marie M Moffatt Miriam F MF Farrall Martin M Bouzigon Emmanuelle E Strachan David P DP Demenais Florence F Lathrop Mark M Cookson William O C M WOCM Richards J Brent JB

PLoS medicine 20170509 5

<h4>Background</h4>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.<h4>Methods and findings</h4>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 ...[more]

PMID: 28486474

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Project description:BackgroundStructural abnormalities in the brain of patients with atopic dermatitis (AD) have been reported; however, the cause has not been determined yet. Herein, we used Mendelian randomization (MR) to reveal the causal effect of AD on brain structure.MethodsThis study utilized summary statistics from genome-wide association studies (GWASs) to investigate a collection of cerebral structural measures, encompassing cortical thickness (CT), cortical surface area (CA), and subcortical volumes in T1 images. A comprehensive GWAS meta-analysis identified a total of 20 independent single nucleotide polymorphisms linked to AD, surpassing the genome-wide significance threshold (p < 5 × 10⁻⁸). MR estimates were aggregated through the application of the inverse variance weighted method. Additional complementary analyses (i.e., MR-Egger and weighted median approaches) were conducted to further assess the robustness of the obtained results. Sensitivity analysis and multivariate MR (MVMR) while adjusting for brain structural changes risk factors (i.e., depression and anxiety) were performed to assess the reliability and stability of observed causality.ResultsGenetically determined AD exhibited a causal link with reduced caudate volumes (IVW-MR: β = -0.186, p = 0.001, p-corrected = 0.009). Furthermore, we identified potential causal associations between AD and reduced CT in the cingulate region (posterior cingulate, IVW-MR: β = -0.065, p = 0.018, p-corrected = 0.551; isthmus cingulate, IVW-MR: β = -0.086, p = 0.003, p-corrected = 0.188), as well as abnormal cortical surface area (CA) in the supramarginal (IVW-MR: β = -0.047, p = 0.044, p-corrected = 0.714) and isthmus cingulate (IVW-MR: β = 0.053, p = 0.018, p-corrected = 0.714). Additional supplementary analyses yielded consistent outcomes. There was no evidence of horizontal pleiotropy. MVMR analysis showed that the causal effects of AD on abnormal brain structure remained significant while adjusting for depression and anxiety.ConclusionThis MR study provided suggestive evidence that decreased caudate nucleus, posterior cingulate cortex, isthmus cingulate cortex and supramarginal gyrus are suggestively associated with higher AD risk. Future investigation into the brain regions is recommended, which helps to clarify the underlying mechanisms and point to new therapies against AD.

Project description:BackgroundObservational studies have suggested the potential associations between atopic dermatitis (AD) and psychiatric disorders. However, the causal relationship between them remains uncertain. This study aimed to evaluate the potential bidirectional causal relationship between AD and psychiatric disorders, including autism spectrum disorder (ASD), major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), anorexia nervosa (AN), Tourette syndrome (TS), schizophrenia, and anxiety.MethodsBidirectional two-sample Mendelian randomization (MR) was employed to elucidate the causality between AD and psychiatric disorders, using summary statistics from the most comprehensive genome-wide association studies conducted on AD (Ncases = 60,653, Ncontrols = 804,329). Psychiatric disorders were derived from the Psychiatric Genomics Consortium and were independent of AD data sources. The MR analysis entailed the implementation of multiple methods, including the inverse variance weighted method, MR-Egger regression method, weighted median method, simple mode method, and weighted mode method.ResultsBidirectional two-sample MR analysis uncovered significant causal associations between AD and severe psychiatric disorders. Specifically, liability to AD was associated with increased risk of ADHD (OR = 1.116; 95% CI: [1.009, 1.234]; P = 0.033) and ASD (OR = 1.131; 95% CI: [1.023, 1.251]; P = 0.016). Additionally, evidence suggested that liability to ADHD (OR = 1.112; 95% CI: [1.094, 1.130]; P = 9.20e-40), liability to AN (OR = 1.1; 95% CI: [1.068, 1.134]; P = 4.45e-10) and liability to BD (OR = 1.067; 95% CI: [1.009, 1.128]; P = 0.023) were associated with an increased risk of AD. Only the causal association between AD and ASD was independent of the reverse effect bias. These causal associations were robust and not affected by biases of heterogeneity and horizontal pleiotropy.ConclusionsOur study emphasizes the significant causal association between AD and an increased risk of ASD, and also identifying BD and AN as risk factors for AD.

Dataset Information

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

Background

Methods and findings

Conclusions

Publications

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

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