Change in hematologic indices over time in pediatric inflammatory bowel disease treated with azathioprin

Azathioprine leads to changes in mean corpuscular volume (MCV) and white blood cell (WBC) indices reflecting efficacy or toxicity. Understanding the interactions between bone marrow stem cells and azathioprine could highlight abnormal response patterns as forerunners for hematologic malignancies. This study gives a statistical description of factors influencing the relationship between MCV and WBC in children with inflammatory bowel disease treated with azathioprine. We found that leukopenia preceded macrocytosis. Macrocytosis is therefore not a good predictor of leukopenia. Further studies will be necessary to determine the subgroup of patients at increased risk of malignancies based on bone marrow response. © 2010 Soman et al., publisher and licensee Adis Data Information BV

Change in hematologic indices over time in pediatric inflammatory bowel disease treated with azathioprine

Azathioprine leads to changes in mean corpuscular volume (MCV) and white blood cell (WBC) indices reflecting efficacy or toxicity. Understanding the interactions between bone marrow stem cells and azathioprine could highlight abnormal response patterns as forerunners for hematologic malig-nancies. This study gives a statistical description of factors influencing the relationship between MCV and WBC in children with inflammatory bowel disease treated with azathioprine. We found that leukopenia preceded macro¬cytosis. Macrocytosis is therefore not a good predictor of leukopenia. Further studies will be necessary to determine the subgroup of patients at increased risk of malignancies based on bone marrow response

Bayesian Classification and Regression Trees for Predicting Incidence of Cryptosporidiosis

Background Classification and regression tree (CART) models are tree-based exploratory data analysis methods which have been shown to be very useful in identifying and estimating complex hierarchical relationships in ecological and medical contexts. In this paper, a Bayesian CART model is described and applied to the problem of modelling the cryptosporidiosis infection in Queensland, Australia. Methodology/Principal Findings We compared the results of a Bayesian CART model with those obtained using a Bayesian spatial conditional autoregressive (CAR) model. Overall, the analyses indicated that the nature and magnitude of the effect estimates were similar for the two methods in this study, but the CART model more easily accommodated higher order interaction effects. Conclusions/Significance A Bayesian CART model for identification and estimation of the spatial distribution of disease risk is useful in monitoring and assessment of infectious diseases prevention and control

Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis.

We genotyped 2,861 cases of primary biliary cirrhosis (PBC) from the UK PBC Consortium and 8,514 UK population controls across 196,524 variants within 186 known autoimmune risk loci. We identified 3 loci newly associated with PBC (at P0.8) with the most associated variant at the locus. We found multiple independent common, low-frequency and rare variant association signals at five loci. Of the 26 independent non-human leukocyte antigen (HLA) signals tagged on the Immunochip, 15 have SNPs in B-lymphoblastoid open chromatin regions in high LD (r2>0.8) with the most associated variant. This study shows how data from dense fine-mapping arrays coupled with functional genomic data can be used to identify candidate causal variants for functional follow-up

Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis

We genotyped 2,861 cases of primary biliary cirrhosis (PBC) from the UK PBC Consortium and 8,514 UK population controls across 196,524 variants within 186 known autoimmune risk loci. We identified 3 loci newly associated with PBC (at P&lt;5×10(-8)), increasing the number of known susceptibility loci to 25. The most associated variant at 19p12 is a low-frequency nonsynonymous SNP in TYK2, further implicating JAK-STAT and cytokine signaling in disease pathogenesis. An additional five loci contained nonsynonymous variants in high linkage disequilibrium (LD; r2&gt;0.8) with the most associated variant at the locus. We found multiple independent common, low-frequency and rare variant association signals at five loci. Of the 26 independent non-human leukocyte antigen (HLA) signals tagged on the Immunochip, 15 have SNPs in B-lymphoblastoid open chromatin regions in high LD (r2&gt;0.8) with the most associated variant. This study shows how data from dense fine-mapping arrays coupled with functional genomic data can be used to identify candidate causal variants for functional follow-up.</p

Dense fine-mapping study identifies new susceptibility loci for primary biliary cirrhosis.

We genotyped 2,861 cases of primary biliary cirrhosis (PBC) from the UK PBC Consortium and 8,514 UK population controls across 196,524 variants within 186 known autoimmune risk loci. We identified 3 loci newly associated with PBC (at P0.8) with the most associated variant at the locus. We found multiple independent common, low-frequency and rare variant association signals at five loci. Of the 26 independent non-human leukocyte antigen (HLA) signals tagged on the Immunochip, 15 have SNPs in B-lymphoblastoid open chromatin regions in high LD (r2>0.8) with the most associated variant. This study shows how data from dense fine-mapping arrays coupled with functional genomic data can be used to identify candidate causal variants for functional follow-up

Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis.

In addition to the HLA locus, six genetic risk factors for primary biliary cirrhosis (PBC) have been identified in recent genome-wide association studies (GWAS). To identify additional loci, we carried out a GWAS using 1,840 cases from the UK PBC Consortium and 5,163 UK population controls as part of the Wellcome Trust Case Control Consortium 3 (WTCCC3). We followed up 28 loci in an additional UK cohort of 620 PBC cases and 2,514 population controls. We identified 12 new susceptibility loci (at a genome-wide significance level of P < 5 × 10⁻⁸) and replicated all previously associated loci. We identified three further new loci in a meta-analysis of data from our study and previously published GWAS results. New candidate genes include STAT4, DENND1B, CD80, IL7R, CXCR5, TNFRSF1A, CLEC16A and NFKB1. This study has considerably expanded our knowledge of the genetic architecture of PBC