Nasal DNA methylation at three CpG sites predicts childhood allergic disease

Childhood allergic diseases, including asthma, rhinitis and eczema, are prevalent conditions that share strong genetic and environmental components. Diagnosis relies on clinical history and measurements of allergen-specific IgE. We hypothesize that a multi-omics model could accurately diagnose childhood allergic disease. We show that nasal DNA methylation has the strongest predictive power to diagnose childhood allergy, surpassing blood DNA methylation, genetic risk scores, and environmental factors. DNA methylation at only three nasal CpG sites classifies allergic disease in Dutch children aged 16 years well, with an area under the curve (AUC) of 0.86. This is replicated in Puerto Rican children aged 9-20 years (AUC 0.82). DNA methylation at these CpGs additionally detects allergic multimorbidity and symptomatic IgE sensitization. Using nasal single-cell RNA-sequencing data, these three CpGs associate with influx of T cells and macrophages that contribute to allergic inflammation. Our study suggests the potential of methylation-based allergy diagnosis

Nasal DNA methylation at three CpG sites predicts childhood allergic disease

Childhood allergic diseases, including asthma, rhinitis and eczema, are prevalent conditions that share strong genetic and environmental components. Diagnosis relies on clinical history and measurements of allergen-specific IgE. We hypothesize that a multi-omics model could accurately diagnose childhood allergic disease. We show that nasal DNA methylation has the strongest predictive power to diagnose childhood allergy, surpassing blood DNA methylation, genetic risk scores, and environmental factors. DNA methylation at only three nasal CpG sites classifies allergic disease in Dutch children aged 16 years well, with an area under the curve (AUC) of 0.86. This is replicated in Puerto Rican children aged 9-20 years (AUC 0.82). DNA methylation at these CpGs additionally detects allergic multimorbidity and symptomatic IgE sensitization. Using nasal single-cell RNA-sequencing data, these three CpGs associate with influx of T cells and macrophages that contribute to allergic inflammation. Our study suggests the potential of methylation-based allergy diagnosis

Using Polarized Spectroscopy to Investigate Order in Thin-Films of Ionic Self-Assembled Materials Based on Azo-Dyes

Three series of ionic self-assembled materials based on anionic azo-dyes and cationic benzalkonium surfactants were synthesized and thin films were prepared by spin-casting. These thin films appear isotropic when investigated with polarized optical microscopy, although they are highly anisotropic. Here, three series of homologous materials were studied to rationalize this observation. Investigating thin films of ordered molecular materials relies to a large extent on advanced experimental methods and large research infrastructure. A statement that in particular is true for thin films with nanoscopic order, where X-ray reflectometry, X-ray and neutron scattering, electron microscopy and atom force microscopy (AFM) has to be used to elucidate film morphology and the underlying molecular structure. Here, the thin films were investigated using AFM, optical microscopy and polarized absorption spectroscopy. It was shown that by using numerical method for treating the polarized absorption spectroscopy data, the molecular structure can be elucidated. Further, it was shown that polarized optical spectroscopy is a general tool that allows determination of the molecular order in thin films. Finally, it was found that full control of thermal history and rigorous control of the ionic self-assembly conditions are required to reproducibly make these materials of high nanoscopic order. Similarly, the conditions for spin-casting are shown to be determining for the overall thin film morphology, while molecular order is maintained

Maternal 17q21 genotype influences prenatal vitamin D effects on offspring asthma/recurrent wheeze

BACKGROUND: Prenatal vitamin D(3) supplementation has been linked to reduced risk of early life asthma/recurrent wheeze. This protective effect appears to be influenced by variations in the 17q21 functional SNP rs12936231 of the child, which regulates the expression of ORMDL3, and for which the high-risk CC-genotype is associated with early-onset asthma. However, this does not fully explain the differential effects of supplementation. We investigated the influence of maternal rs12936231 genotype variation on the protective effect of prenatal vitamin D(3) supplementation against offspring asthma/recurrent wheeze. METHODS: We determined the rs12936231 genotype of mother-child pairs from two randomized-controlled trials: the Vitamin D Antenatal Asthma Reduction Trial (VDAART, n=613) and the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC(2010), n=563) to examine the effect of maternal genotype variation on offspring asthma/recurrent wheeze at age 0–3 years between groups who received high-dose prenatal vitamin D(3) supplementation versus placebo. RESULTS: Offspring of mothers with low-risk GG-genotype or GC-genotype who received high-dose vitamin D(3) supplementation had a significantly reduced risk of asthma/recurrent wheeze when compared to the placebo group (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.37–0.77; P<0.001 for VDAART and HR, 0.56; 95% CI, 0.35–0.92; P=0.021 for COPSAC(2010)), whereas no difference was observed among the offspring of mothers with high-risk CC-genotype (HR, 1.05; 95% CI, 0.61–1.84; P=0.853 for VDAART and HR, 1.11; 95% CI, 0.54–2.28; P=0.785 for COPSAC(2010)). CONCLUSION: Maternal 17q21 genotype has an important influence on the protective effects of prenatal vitamin D(3) supplementation against offspring asthma/recurrent wheeze