Race and Inflammatory Bowel Disease in an Urban Healthcare System

Inflammatory bowel disease (IBD) is increasingly common among non-Caucasian populations, but interracial differences in disease characteristics and management are not well-characterized. We tested the hypothesis that disease characteristics and management vary by race among IBD patients in an ethnically diverse healthcare system. A retrospective study of the safety net healthcare system of San Francisco, CA, from 1996 to 2009 was undertaken. Patient records with International Classification of Diseases, 9th Revision (ICD9) codes 555.xx, 556.xx, and 558.xx were reviewed. Adult patients with confirmed IBD diagnoses were included. Interracial variations in disease characteristics and management were assessed broadly; focused between-race comparisons identified specific differences. The 228 subjects included 77 (33.4%) with Crohn’s disease (CD), 150 (65.8%) with ulcerative colitis, and 1 (0.4%) with IBD, type unclassified. The race distribution included 105 (46.1%) white, 34 (14.9%) black, 35 (15.4%) Hispanic, and 51 (22.4%) Asian subjects. Asians and Hispanics were diagnosed at older ages (41.0 and 37.1 years, respectively) and had shorter disease durations (5.4 and 5.2 years, respectively) than whites (30.5 years at diagnosis and 8.6 years duration, P < 0.05) and blacks (31.7 years at diagnosis and 12.1 years duration, P < 0.05). CD was more common among blacks (50% of subjects) than Asians (25.5% of subjects, P = 0.015). The Montreal classification of IBD was similar among races. Hispanics were less likely than others to be treated with 5-aminosalicylates (5-ASA), immunomodulators, and steroids. Medical and surgical management was otherwise similar among races. Modest race-based differences in IBD characteristics exist in this racially diverse healthcare system, but the management of IBD is similar among race groups

Genetic sharing and heritability of paediatric age of onset autoimmune diseases

Autoimmune diseases (AIDs) are polygenic diseases affecting 7–10 % of the population in the Western Hemisphere with few effective therapies. Here, we quantify the heritability of paediatric AIDs (pAIDs)

Meta-analysis of shared genetic architecture across ten pediatric autoimmune diseases

Genome-wide association studies (GWASs) have identified hundreds of susceptibility genes, including shared associations across clinically distinct autoimmune diseases. We performed an inverse χ(2) meta-analysis across ten pediatric-age-of-onset autoimmune diseases (pAIDs) in a case-control study including more than 6,035 cases and 10,718 shared population-based controls. We identified 27 genome-wide significant loci associated with one or more pAIDs, mapping to in silico-replicated autoimmune-associated genes (including IL2RA) and new candidate loci with established immunoregulatory functions such as ADGRL2, TENM3, ANKRD30A, ADCY7 and CD40LG. The pAID-associated single-nucleotide polymorphisms (SNPs) were functionally enriched for deoxyribonuclease (DNase)-hypersensitivity sites, expression quantitative trait loci (eQTLs), microRNA (miRNA)-binding sites and coding variants. We also identified biologically correlated, pAID-associated candidate gene sets on the basis of immune cell expression profiling and found evidence of genetic sharing. Network and protein-interaction analyses demonstrated converging roles for the signaling pathways of type 1, 2 and 17 helper T cells (TH1, TH2 and TH17), JAK-STAT, interferon and interleukin in multiple autoimmune diseases

Production of charged pions, kaons and protons at large transverse momenta in pp and Pb–Pb collisions at sNN=2.76\sqrt{s_{NN}}=2.76 TeV

Transverse momentum spectra of pi(+/-), K-+/- and p((p) over bar) up to p(T) = 20 GeV/c at mid-rapidity in pp, peripheral (60-80%) and central (0-5%) Pb-Pb collisions at v root s(NN) = 2.76 TeV have been measured using the ALICE detector at the Large Hadron Collider. The proton-to-pion and the kaon-to-pionratios both show a distinct peak at p(T) approximate to 3 GeV/c in central Pb-Pb collisions. Below the peak, p(T) 10 GeV/c particle ratios in pp and Pb-Pb collisions are in agreement and the nuclear modification factors for pi(+/-), K-+/- and p((p) over bar) indicate that, within the systematic and statistical uncertainties, the suppression is the same. This suggests that the chemical composition of leading particles from jets in the medium is similar to that of vacuum jets

Centrality dependence of the pseudorapidity density distribution for charged particles in Pb\u2013Pb collisions at 1asNN = 2.76 TeV

We present the first wide-range measurement of the charged-particle pseudorapidity density distribution, for different centralities (the 0\u20135%, 5\u201310%, 10\u201320%, and 20\u201330% most central events) in Pb\u2013Pb collisions at 1asNN = 2.76 TeV at the LHC. The measurement is performed using the full coverage of the ALICE detectors, 125.0 < \u3b7 < 5.5, and employing a special analysis technique based on collisions arising from LHC \u2018satellite\u2019 bunches. We present the pseudorapidity density as a function of the number of participating nucleons as well as an extrapolation to the total number of produced charged particles (Nch = 17 165 \ub1 772 for the 0\u20135% most central collisions). From the measured dNch/d\u3b7 distribution we derive the rapidity density distribution, dNch/dy, under simple assumptions. The rapidity density distribution is found to be significantly wider than the predictions of the Landau model. We assess the validity of longitudinal scaling by comparing to lower energy results from RHIC. Finally the mechanisms of the underlying particle production are discussed based on a comparison with various theoretical models

Production of charged pions, kaons and protons at large transverse momenta in pp and Pb–Pb collisions at sNN=2.76\sqrt{s_{NN}}=2.76 TeV

Transverse momentum spectra of pi(+/-), K-+/- and p((p) over bar) up to p(T) = 20 GeV/c at mid-rapidity in pp, peripheral (60-80%) and central (0-5%) Pb-Pb collisions at v root s(NN) = 2.76 TeV have been measured using the ALICE detector at the Large Hadron Collider. The proton-to-pion and the kaon-to-pionratios both show a distinct peak at p(T) approximate to 3 GeV/c in central Pb-Pb collisions. Below the peak, p(T) 10 GeV/c particle ratios in pp and Pb-Pb collisions are in agreement and the nuclear modification factors for pi(+/-), K-+/- and p((p) over bar) indicate that, within the systematic and statistical uncertainties, the suppression is the same. This suggests that the chemical composition of leading particles from jets in the medium is similar to that of vacuum jets

Centrality, rapidity and transverse momentum dependence of J/\u3c8 suppression in Pb-Pb collisions at 1asNN= 2.76TeV

The inclusive J/.nuclear modification factor (R-AA) in Pb-Pb collisions at root(NN)-N-S = 2.76TeVhas been measured by ALICE as a function of centrality in the e+ e-decay channel at mid-rapidity (| y| < 0.8) and as a function of centrality, transverse momentum and rapidity in the + -decay channel at forward-rapidity (2.5 < y < 4). The J/.yields measured in Pb-Pb are suppressed compared to those in ppcollisions scaled by the number of binary collisions. The RAAintegrated over a centrality range corresponding to 90% of the inelastic Pb-Pb cross section is 0.72 - 0.06(stat.) - 0.10(syst.) at mid-rapidity and 0.58 - 0.01(stat.) - 0.09(syst.) at forward-rapidity. At low transverse momentum, significantly larger values of RAAare measured at forward-rapidity compared to measurements at lower energy. These features suggest that a contribution to the J/.yield originates from charm quark (re) combination in the deconfined partonic medium

Deep Resequencing of GWAS Loci Identifies Rare Variants in CARD9, IL23R and RNF186 That Are Associated with Ulcerative Colitis

<p>Genome-wide association studies and follow-up meta-analyses in Crohn's disease (CD) and ulcerative colitis (UC) have recently identified 163 disease-associated loci that meet genome-wide significance for these two inflammatory bowel diseases (IBD). These discoveries have already had a tremendous impact on our understanding of the genetic architecture of these diseases and have directed functional studies that have revealed some of the biological functions that are important to IBD (e.g. autophagy). Nonetheless, these loci can only explain a small proportion of disease variance (similar to 14% in CD and 7.5% in UC), suggesting that not only are additional loci to be found but that the known loci may contain high effect rare risk variants that have gone undetected by GWAS. To test this, we have used a targeted sequencing approach in 200 UC cases and 150 healthy controls (HC), all of French Canadian descent, to study 55 genes in regions associated with UC. We performed follow-up genotyping of 42 rare non-synonymous variants in independent case-control cohorts (totaling 14,435 UC cases and 20,204 HC). Our results confirmed significant association to rare non-synonymous coding variants in both IL23R and CARD9, previously identified from sequencing of CD loci, as well as identified a novel association in RNF186. With the exception of CARD9 (OR = 0.39), the rare non-synonymous variants identified were of moderate effect (OR = 1.49 for RNF186 and OR = 0.79 for IL23R). RNF186 encodes a protein with a RING domain having predicted E3 ubiquitin-protein ligase activity and two transmembrane domains. Importantly, the disease-coding variant is located in the ubiquitin ligase domain. Finally, our results suggest that rare variants in genes identified by genome-wide association in UC are unlikely to contribute significantly to the overall variance for the disease. Rather, these are expected to help focus functional studies of the corresponding disease loci.</p>