Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants

Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size >39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NFκB cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8+ T-cells and CD4+ T-cells including TH0, TH1 and TH17). The identified loci explain ∼28% of the genetic heritability and generate a discriminatory genetic risk score (AUC=0.76 in our sample) that is significantly correlated with age at onset (p=2 × 10−89). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis

Design and construction of the MicroBooNE detector

This paper describes the design and construction of the MicroBooNE liquid argon time projection chamber and associated systems. MicroBooNE is the first phase of the Short Baseline Neutrino program, located at Fermilab, and will utilize the capabilities of liquid argon detectors to examine a rich assortment of physics topics. In this document details of design specifications, assembly procedures, and acceptance tests are reported

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Diode laser spectroscopy using a calibration free phasor decomposition approach with RAM nulling

A limiting factor of tunable diode laser spectroscopy (TDLS) analysis is the large unwanted residual amplitude modulation (RAM) background present on the recovered 1st harmonic signal. A novel approach to remove the background RAM will be presented. This new technique will be used alongside the phasor decomposition method (PDM) [1], a calibration free technique for recovery of the absolute gas absorption line-shape. The RAM nulling method developed, successfully removes the background by optical cancellation. This is achieved by placing a fibre delay line, which introduces a π phase change in the modulation signal, in parallel with the gas cell line. When these lines are coupled together the background signals are at anti-phase and hence cancel each other. The main benefit being that measurement sensitivity can be increased. Results illustrating RAM nulling whilst using the PDM technique for absorption line-shape recovery will be presented. Figure 1 shows a recorded PDM measurement illustrating the difference with and without RAM Nulling

Recovery of gas absorption lineshapes using TDLS at arbitrary modulation indices

Poster presentation on the recovery of gas absorption lineshapes using TDLS at arbitrary modulation indices

Recovery of absolute gas absorption lineshapes using TDLS at arbitrary modulation indices

Presentation submitted to the International Conference on Field Laser Applications in Industry and Research (FLAIR), held in Grainau, Germany, on the 6-11 September 2009. Exhibition & Poster Session I “Hotel am Badersee

Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility

10.1038/ncomms7916Nature Communications