Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10-8), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding

Interactive proteogenomic exploration of response to Fusarium head blight in oat varieties with different resistance

Fusarium species are cereal pathogens that cause the Fusarium Head Blight (FHB) disease. FHB can reduce yield, cause mycotoxin accumulation in the grain and reduce germination efficiency of the harvested seeds. Understanding the biochemical interactions between the host plants and the pathogen is crucial for controlling the disease and for the development of cultivars with improved tolerance to FHB. Here, we studied morphological and proteomic differences between the susceptible oat variety Belinda and the more resistant variety Argamak using variety-specific transcriptome assemblies as references. Measurements of deoxynivalenol toxin levels confirmed the partial resistance in Argamak and the susceptibility in Belinda. To jointly investigate the proteomics- and sequence data, we developed an RShiny-based interface for interactive exploration of the dataset using univariate and multivariate statistics. When applying this interface to the dataset, quantitative protein differences between Belinda and Argamak were detected, and eighteen peptides were found uniquely in Argamak during infection, among them several lipoxygenases. Such proteins can be developed as markers for Fusarium resistance breeding. In conclusion, this study provides the first proteogenomic insight on molecular Fusarium-oat interactions at both morphological and molecular levels and the data are openly available through an interactive interface for further inspection. SIGNIFICANCE: Fusarium head blight causes widespread damage to crops, and chronic and acute toxicity to human and livestock due to the accumulation of toxins during infection. In the present study, two oat varieties with differing resistance were challenged with Fusarium to understand the disease better, and studied both at morphological and molecular levels, identifying proteins which could play a role in the defense mechanism. Furthermore, a proteogenomics approach allows joint profiling of expression and sequence level differences to identify potentially functionally differing mutations. Here such analysis is made openly available through an interactive interface which allows other scientists to draw further findings from the data. This study may both serve as a basis for understanding oat disease response and developing breeding markers for Fusarium resistant oat and future proteogenomic studies using the interactive approach described

Immunomodulatory effects of oak dust exposure in a murine model of allergic asthma.

Repeated airway exposure to wood dust has been reported to cause adverse respiratory effects such as asthma and chronic bronchitis. In our recent study, we found that exposure of mice to oak dust induced more vigorous lung inflammation compared to birch dust exposure. In the present study, we assessed the immunomodulatory effects of repeated intranasal exposure to oak dust both in nonallergic and in ovalbumin-sensitized, allergic mice. Allergen-induced influx of eosinophils and lymphocytes was seen in the lungs of allergic mice. Oak dust exposure elicited infiltration of neutrophils, lymphocytes, and macrophages in nonallergic mice. Interestingly, oak dust-induced lung neutrophilia as well as oak dust-induced production of the proinflammatory cytokine TNF-alpha and chemokine CCL3 were significantly suppressed in allergic mice. On the other hand, allergen-induced expression of IL-13 mRNA and protein was significantly reduced in oak dust-exposed allergic mice. Finally, allergen-induced airway hyperreactivity to inhaled metacholine was significantly suppressed in oak dust-exposed allergic mice. The present results suggest that repeated airway exposure to oak dust can regulate pulmonary inflammation and airway responses depending on the immunological status of the animal