GWAS for Systemic Sclerosis Identifies Multiple Risk Loci and Highlights Fibrotic and Vasculopathy Pathways

Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.Funding: This work was supported by Spanish Ministry of Economy and Competitiveness (grant ref. SAF2015-66761-P), Consejeria de Innovacion, Ciencia y Tecnologia, Junta de Andalucía (P12-BIO-1395), Ministerio de Educación, Cultura y Deporte through the program FPU, Juan de la Cierva fellowship (FJCI-2015-24028), Red de Investigación en Inflamación y Enfermadades Reumaticas (RIER) from Instituto de Salud Carlos III (RD16/0012/0013), and Scleroderma Research Foundation and NIH P50-HG007735 (to H.Y.C.). H.Y.C. is an Investigator of the Howard Hughes Medical Institute. PopGen 2.0 is supported by a grant from the German Ministry for Education and Research (01EY1103). M.D.M and S.A. are supported by grant DoD W81XWH-18-1-0423 and DoD W81XWH-16-1-0296, respectively

Analysis of fracture induced scattering of microseismic shear-waves

Fractures are pervasive features within the Earth’s crust and have a significant influence on the multi-physical response of the subsurface. The presence of coherent fracture sets often leads to observable seismic scattering enabling seismic techniques to remotely locate and characterise fracture systems. In this study, we confirm the general scale-dependence of seismic scattering and provide new results specific to shear-wave propagation. We do this by generating full waveform synthetics using finite-difference wave simulation within an isotropic background model containing explicit fractures. By considering a suite of fracture models having variable fracture density and fracture size, we examine the widening effect of wavelets due to scattering within a fractured medium by using several different approaches, such as root-mean-square envelope analysis, shear-wave polarisation distortion, differential attenuation analysis and peak frequency shifting. The analysis allows us to assess the scattering behavior of parametrised models in which the propagation direction is either normal or parallel to the fracture surfaces. The quantitative measures show strong observable deviations for fractures size on the order of or greater than the dominant seismic wavelength within the Mie and geometric scattering regime for both propagation normal and parallel to fracture strike. The results suggest that strong scattering is symptomatic of fractures having size on the same order of the probing seismic wave

Incorporating efficiency in hospital-capacity planning in Germany

Hospital capacity planning, Hospital efficiency, Data envelopment analysis, C61, H51, I18,