Lung eQTLs to Help Reveal the Molecular Underpinnings of Asthma

Genome-wide association studies (GWAS) have identified loci reproducibly associated with pulmonary diseases; however, the molecular mechanism underlying these associations are largely unknown. The objectives of this study were to discover genetic variants affecting gene expression in human lung tissue, to refine susceptibility loci for asthma identified in GWAS studies, and to use the genetics of gene expression and network analyses to find key molecular drivers of asthma. We performed a genome-wide search for expression quantitative trait loci (eQTL) in 1,111 human lung samples. The lung eQTL dataset was then used to inform asthma genetic studies reported in the literature. The top ranked lung eQTLs were integrated with the GWAS on asthma reported by the GABRIEL consortium to generate a Bayesian gene expression network for discovery of novel molecular pathways underpinning asthma. We detected 17,178 cis- and 593 trans- lung eQTLs, which can be used to explore the functional consequences of loci associated with lung diseases and traits. Some strong eQTLs are also asthma susceptibility loci. For example, rs3859192 on chr17q21 is robustly associated with the mRNA levels of GSDMA (P = 3.55 × 10(-151)). The genetic-gene expression network identified the SOCS3 pathway as one of the key drivers of asthma. The eQTLs and gene networks identified in this study are powerful tools for elucidating the causal mechanisms underlying pulmonary disease. This data resource offers much-needed support to pinpoint the causal genes and characterize the molecular function of gene variants associated with lung diseases

Health system strengthening in fragile and conflict-affected states: a call to action.

Although the speed of global development has been impressive, not all countries have developed at the same pace. The World Bank Group (WBG) report that Fragile and Conflict-Affected States (FCAS) are those countries that have lower health and development outcomes, and risk not being able to achieve Sustainable Development Goals (SDGs) in the next few years. Health systems play an important role in building capacity and infrastructure that can lead towards fulfilling the SDGs. In this editorial, we set the context, and launch a call to action, for a BMC Health Service Research Collection titled "Health services and systems in fragile and conflict-affected regions"

Elevage bovin et environnement Prevenir les risques de nuisance et de pollution

Available from INIST (FR), Document Supply Service, under shelf-number : RP 185 (4171) / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEMinistere de l'Environnement, 75 - Paris (France). Service de l'Environnement Industriel (SEI)FRFranc

Role of tumor necrosis factor alpha in asthma

Asthma is a heterogeneous disease in which various cytokines orchestrate airway inflammation. Tumor necrosis alpha (TNF-alpha) is a proinflammatory cytokine that has been implicated in the modulation of inflammation in various diseases, including asthma. Although TNF-alpha blocking strategies have been an effective therapeutic modality in diseases such as rheumatoid arthritis, their role in asthma and the effects of the blockade in asthma is poorly understood. This article examines the role of TNF-alpha in asthma and the effects of blocking TNF-alpha as a possible therapeutic option in patients with severe corticosteroid-dependent asthma

Relative expression of <i>GSDMA</i> and <i>GSDMB</i>.

<p>Primary human airway epithelial cells in monolayer culture were analyzed for; (a) the relative abundance of mRNA for <i>GSDMA</i> and <i>GSDMB</i> (n = 7) and (b) Protein expression of <i>GSDMA</i> and <i>GSDMB</i> by Western blot normalized to expression of β-tubulin (n = 10). (c) Representative image of <i>GSDMA</i> expression in human conducting airway by immunohistochemistry, which shows expression of <i>GSDMA</i> in both basal and apical cells within the airway epithelium.</p

Lung eQTLs found on chromosome 17q21.

<p>(a) The upper panel is a region of chromosome 17q21 from the UCSC browser showing the genes located in this region. The next panel shows the results from the GABRIEL consortium <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003029#pgen.1003029-Moffatt1" target="_blank">[9]</a> (each bar represents a SNP and the y-axis shows −log₁₀<i>P</i> values for association with asthma). The following three panels show the lung eQTL results for expression levels of <i>ORMDL3</i> (blue bars), <i>GSDMB</i> (green bars), and <i>GSDMA</i> (red bars), respectively. The y-axis represents −log₁₀<i>P</i> values derived from the meta-analysis of gene expression. The black horizontal lines are drawn at <i>P</i> = 0.05. (b) Boxplots of lung gene expression levels for GSDMA according to genotype groups for SNPs rs3859192 and rs7216389 in 1,111 subjects.</p