20 research outputs found
Genome-wide association study of primary sclerosing cholangitis identifies new risk loci and quantifies the genetic relationship with inflammatory bowel disease.
Primary sclerosing cholangitis (PSC) is a rare progressive disorder leading to bile duct destruction; ∼75% of patients have comorbid inflammatory bowel disease (IBD). We undertook the largest genome-wide association study of PSC (4,796 cases and 19,955 population controls) and identified four new genome-wide significant loci. The most associated SNP at one locus affects splicing and expression of UBASH3A, with the protective allele (C) predicted to cause nonstop-mediated mRNA decay and lower expression of UBASH3A. Further analyses based on common variants suggested that the genome-wide genetic correlation (rG) between PSC and ulcerative colitis (UC) (rG = 0.29) was significantly greater than that between PSC and Crohn's disease (CD) (rG = 0.04) (P = 2.55 × 10-15). UC and CD were genetically more similar to each other (rG = 0.56) than either was to PSC (P < 1.0 × 10-15). Our study represents a substantial advance in understanding of the genetics of PSC
A multi-scenario based micro seismic hazard assessment of the Bhuj City, western India incorporating geophysical and geotechnical parameters
The micro-seismic hazard assessment (micro-SHA) of the Bhuj city (highest seismic zone V) has been accomplished considering seismotectonic as well as shallow subsurface modeling through geophysical (multi-channel analysis of surface waves (MASW) survey at 19 sites) and geotechnical parameters from 28 boreholes distributed in the entire Bhuj city. The average shear wave velocity through the MASW survey at 30 m depth (VS30) is estimated in the range of 400–915 m/s (NEHRP C-type and B-type soil classes). Seismotectonically justified a total of 54 scenario-earthquakes (SEQs) along all major faults have been considered to evaluate the strong ground motion at generic soil level having a shear wave velocity of 760 m/s and depth of 12–28 m. The surface level strong motion (SM) has been estimated through ground response analysis preparing soil models along all boreholes. The PGA at the surface in Bhuj city has been estimated in the range of 528 cm/s2 to 1020 cm/s2; highest in the central-western part of the Bhuj city where clay with high plasticity is present. The mean-spectral acceleration over the study area for 0.2 s (corresponding to 1-2 story), 0.55 s (4-5 story), 1sec (high rise) and 1.25 s period (large structures) are prepared at the surface from all scenario earthquakes. The amplification of SM in the Bhuj city is computed in the range of 1.7–3.7