References of "Van Steen, Kristel"
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See detailRestoration Of B Cells Correlates With Clinical Response To Anti-Tnf Therapy
Li, Z; Vermeire, S; Bullens, D et al

Poster (2012, October)

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See detailIntegrating biological information in genome-wide association interaction (GWAI) studies.
Gusareva, Elena ULg; Van Steen, Kristel ULg

Poster (2012, May 30)

Genome-wide association (GWA) studies of Crohn's disease have identified numerous genes. However, a substantial portion of the heritability of this disease remains unexplained. Some gene variants, not ... [more ▼]

Genome-wide association (GWA) studies of Crohn's disease have identified numerous genes. However, a substantial portion of the heritability of this disease remains unexplained. Some gene variants, not detectable via main effects GWA study, may manifest themselves only in interaction with other variants. To search for interacting genes involved in the regulation of Crohn's disease, we performed GWA epistasis screening in a large human cohort (1851 cases/2938 controls) belonging to the Wellcome Trust Case Control Consortium (WTCCC). All subjects were genotyped with the GeneChip 500K Mapping Array Set (Affymetrix chip). SNPs that passed our quality control (359,479 SNPs) were processed in Biofilter (a software package that looks for candidate epistatic genes contributing to disease risk) giving rise to 14,185 SNPs. Subsequent MB-MDR epistasis screening, highlighted evidence for statistical epistasis for 6 SNP pairs. Four of these pairs involve interaction on between the HTR3B and USP28 genes (chromosome 11). One pair involves an interaction between the SLED1 and ACSL1 genes (chromosome 4). Another pair involves an interaction between PTPN22 (chromosome 1) and a SNP located between USPL1 and ALOX5AP (chromosome 13). Notably, when mapped to the same genomic regions, the interacting SNPs were not in linkage disequilibrium (r^2 < 0.11). All results were corrected for potential main SNP effects and were corrected for multiple testing on 7072 SNPs (i.e., 25,003,056 pairs). We investigated the consistency of these findings using different methodologies, including information-based, LD comparison-based and regression-based approaches. We also investigated the utility of using prior information from biological interaction data bases in novel epistasis discoveries, as well as the utility of biological data bases in interpreting a posterior identified statistical epistasis pairs. Our findings may provide new leads on important pathways involved in Crohn's disease. [less ▲]

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See detailFactors determining therapeutic strategy at diagnosis and evolution of disease severity in a cohort of Belgian pediatric Crohn's disease patients (BELCRO)
De Greef, E; Mahachie John, Jestinah; Hoffman, I et al

in Gastroenterology (2012)

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See detailSequential T2 Relaxometry as a Non-Invasive Assessment of Transmural Inflammation in a Murine Model of Chronically Relapsing Colitis
Breynaert, C; Dresselaers, T; Cremer, J et al

Poster (2012, May)

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See detailRepeated cycles of DSS inducing a chronically relapsing inflammation: a novel model to study fibrosis using in vivo MRI T2 relaxometry
Breynaert, C; Dresselaers, T; Cremer, J et al

Poster (2012, May)

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See detailApplication of mixed polygenic model to control for cryptic/genuine relatedness and population stratification.
Gusareva, Elena ULg; Mahachie John, Jestinah ULg; Isaacs, Aaron et al

Poster (2012, March 12)

In genome-wide association studies (GWAs), population stratification may cause inflated type I errors and overly-optimistic test results, when not properly corrected for. During the past decade, several ... [more ▼]

In genome-wide association studies (GWAs), population stratification may cause inflated type I errors and overly-optimistic test results, when not properly corrected for. During the past decade, several methods have been proposed for association testing in the presence of population stratification. Among these, principal components-based approaches are the most popular. Principal component analysis (PCA) allows data transformation to a new coordinate system such that the projection of the data along the first new coordinate (called the PC1) has the largest variance; the second PC has the second largest variance, and so on. In practice, two components are usually enough to adjust or to control for population stratification. They can easily be included in parametric association models as covariates. Despite the success of this strategy, there are still some caveats which need further attention. Among these are that principal component-based methods generally do not account for cryptic relatedness (kinship) between supposedly unrelated individuals, are not straightforwardly adapted to accommodate family-based designs or mixtures of families and unrelated individuals, and do not always take proper account of the trait under investigation. In this work, we present an easy-to-use alternative that addresses the aforementioned issues. For quantitative traits, we propose to first use the mixed polygenic model (possibly taking into account important non-genetic confounders as covariates), second to derive “polygenic” residuals from this model – hereby removing genomic kinship relationships, and third to consider these residuals as new traits in a classical genome-wide QTL analysis for “unrelated individuals”. The polygenic component of the aforementioned mixed polygenic model describes the contribution from multiple independently segregating genes, all having a small additive effect on the trait under investigation. Via an extensive simulation study, with various settings of population stratification and admixture, we show that this approach not only removes most of the “relatedness” between individuals (cryptic relatedness or known relatedness), but also removes most of the remaining substructures caused by population stratification or admixture. As a proof of concept, we demonstrate the efficiency of this robust method to control for population stratification on real-life genome-scale data from the SNP Health Association Resource (SHARe) Asthma Resource project (SHARP) (dbGaP accession number phs000166.v2.p1). We also provide leads to extend this method to dichotomous traits. [less ▲]

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See detailGenetic and functional evidence for a role of CYLD in Crohn’s Disease: results from a European consortium
Cleynen, I; Vazeille, E; Artieda, M et al

in Journal of Crohn’s and Colitis [=JCC] (2012)

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See detailMultiple functional variants at the 3p21 locus contribute to ulcerative colitis: Results from a European consortium
Cleynen, I; Artieda, M; Verspaget, H et al

in Journal of Crohn’s and Colitis [=JCC] (2012)

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See detailRepeated cycles of DSS inducing a chronically relapsing inflammation: A novel model to study fibrosis using in vivo MRI T2 relaxometry
Breynaert, C; Dresselaers, T; Cremer, J et al

Poster (2012, February)

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See detailLower-Order Effects Adjustment in Quantitative Traits Model-Based Multifactor Dimensionality Reduction
Mahachie John, Jestinah ULg; Cattaert, Tom ULg; Van Lishout, François ULg et al

in PLoS ONE (2012)

Identifying gene-gene interactions or gene-environment interactions in studies of human complex diseases remains a big challenge in genetic epidemiology. An additional challenge, often forgotten, is to ... [more ▼]

Identifying gene-gene interactions or gene-environment interactions in studies of human complex diseases remains a big challenge in genetic epidemiology. An additional challenge, often forgotten, is to account for important lower-order genetic effects. These may hamper the identification of genuine epistasis. If lower-order genetic effects contribute to the genetic variance of a trait, identified statistical interactions may simply be due to a signal boost of these effects. In this study, we restrict attention to quantitative traits and bi-allelic SNPs as genetic markers. Moreover, our interaction study focuses on 2- way SNP-SNP interactions. Via simulations, we assess the performance of different corrective measures for lower-order genetic effects in Model-Based Multifactor Dimensionality Reduction epistasis detection, using additive and co-dominant coding schemes. Performance is evaluated in terms of power and familywise error rate. Our simulations indicate that empirical power estimates are reduced with correction of lower-order effects, likewise familywise error rates. Easy-to-use automatic SNP selection procedures, SNP selection based on ‘‘top’’ findings, or SNP selection based on p-value criterion for interesting main effects result in reduced power but also almost zero false positive rates. Always accounting for main effects in the SNP-SNP pair under investigation during Model-Based Multifactor Dimensionality Reduction analysis adequately controls false positive epistasis findings. This is particularly true when adopting a co-dominant corrective coding scheme. In conclusion, automatic search procedures to identify lower-order effects to correct for during epistasis screening should be avoided. The same is true for procedures that adjust for lower-order effects prior to Model-Based Multifactor Dimensionality Reduction and involve using residuals as the new trait. We advocate using ‘‘on-the-fly’’ lower-order effects adjusting when screening for SNP-SNP interactions using Model-Based Multifactor Dimensionality Reduction analysis. [less ▲]

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See detailFactors determining therapeutic strategy at diagnosis and evolution of disease severity in a cohort of Belgian pediatric Crohn’s disease patients (BELCRO)
De Greef, E; Mahachie John, Jestinah; Hoffman, I et al

in Acta Gastro-Enterologica Belgica (2012)

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See detailSafety And Cost Of Infliximab For The Treatment Of Belgian Pediatric Patients With Crohn’s Disease
De Greef, E; Hoffman, I; D'haens, G et al

in Journal of Crohn’s and Colitis (2012)

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See detailEffects of domperidone on QTc interval in infants
Vieira, MC; Miyague, NI; Van Steen, Kristel ULg et al

in Acta Paediatrica (2012), 101(5), 494-496

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See detailSafety and cost of infliximab for the treatment of Belgian pediatric patients with Crohn's disease.
De Greef, E.; Hoffman, I.; D'Haens, G. et al

in Acta Gastro-Enterologica Belgica (2012), 75(4), 425-31

Biologicals have become an important component in the treatment of Crohn's disease in children. Their increased and long term use raises safety concerns. We describe safety and cost of infliximab in ... [more ▼]

Biologicals have become an important component in the treatment of Crohn's disease in children. Their increased and long term use raises safety concerns. We describe safety and cost of infliximab in Belgian pediatric Crohn's disease patients. All patients on infliximab as part of the present or past treatment for Crohn's Disease until January 1st 2011 were selected from an existing database. Information on disease phenotype, medication and adverse events were extracted. Adverse events occurred in 25.9% of patients exposed to infliximab of which 29.6% were severe. In total 31.7% of patients stopped infliximab therapy. The main reasons for discontinuation were adverse events in 45.4% and loss of response in 30.3%. No malignancies or lethal complications occurred over this 241 patient year observation period. Immunomodulators were concomitant medication in 75% of patients and were discontinued subsequently in 38.4% of them. The cost of infliximab infusions per treated patient per year in the Belgian health care setting is approximately 9 474 euro, including only medication and hospital related costs. Even though infliximab is relatively safe in pediatric CD on the short term, close follow-up and an increased awareness of the possible adverse reactions is highly recommended. Adverse reactions appeared in 25.9% of all patients and were the main reason for discontinuation. Treatment cost has to be balanced against efficacy and modifications in disease course. In the Belgian health care system, the medication is available to all patients with moderate to severe CD. [less ▲]

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See detailDoes pet ownership in infancy lead to asthma or allergy at school age? Pooled analysis of individual participant data from 11 European birth cohorts.
Lødrup Carlsen, Karin; Roll, Stephanie; Carlsen, Kai-Håkon et al

in PLoS ONE (2012)

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See detailInference and comparison of different genetic stratification techniques
Maus, Bärbel ULg; Génin, Emmanuelle; Mahachie John, Jestinah ULg et al

Conference (2012)

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See detailClustering of Crohn’s disease patients: Identification of sub-phenotypes and population stratification
Maus, Bärbel ULg; Génin, Emmanuelle; Mahachie John, Jestinah ULg et al

in Genetic Epidemiology (2012), 36(7), 729

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See detailSpecific IgE against Staphylococcus aureus enterotoxins: An independent risk factor for asthma
Bachert, C.; Van Steen, Kristel ULg; Zhang, N. et al

in Journal of Allergy and Clinical Immunology (The) (2012), 130(2), 376-3818

Background: The role of IgE in patients with severe asthma is not fully understood. Objective: We sought to investigate whether IgE to Staphylococcus aureus enterotoxins might be relevant to disease ... [more ▼]

Background: The role of IgE in patients with severe asthma is not fully understood. Objective: We sought to investigate whether IgE to Staphylococcus aureus enterotoxins might be relevant to disease severity in adult asthmatic patients. Methods: Specific IgE antibody concentrations in serum against enterotoxins, grass pollen (GP), and house dust mite allergens and total IgE levels were measured in adult cohorts of 69 control subjects, 152 patients with nonsevere asthma, and 166 patients with severe asthma. Severe asthma was defined as inadequately controlled disease despite high-dose inhaled corticosteroids plus at least 2 other controller therapies, including oral steroids. Results: Enterotoxin IgE positivity was significantly greater in patients with severe asthma (59.6%) than in healthy control subjects (13%, P < .001). Twenty-one percent of patients with severe asthma with enterotoxin IgE were considered nonatopic. Logistic regression analyses demonstrated significantly increased risks for enterotoxin IgE-positive subjects to have any asthma (OR, 7.25; 95% CI, 2.7-19.1) or severe asthma (OR, 11.09; 95% CI, 4.1-29.6) versus enterotoxin IgE-negative subjects. The presence of GP or house dust mite IgE antibodies was not associated with either significantly increased risk for asthma or severity. Oral steroid use and hospitalizations were significantly increased in patients with enterotoxin IgE and nonatopic asthma. GP IgE was associated with a higher FEV 1 percent predicted value, and enterotoxin IgE was associated with a lower FEV 1 percent predicted value. Conclusions: Staphylococcal enterotoxin IgE antibodies, but not IgE against inhalant allergens, are risk factors for asthma severity. We hypothesize that the presence of enterotoxin IgE in serum indicates the involvement of staphylococcal superantigens in the pathophysiology of patients with severe asthma. © 2012 American Academy of Allergy, Asthma & Immunology. [less ▲]

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See detailChallenges and opportunities in genome-wide environmental interaction (GWEI) studies.
Aschard, Hugues; Lutz, Sharon; Maus, Bärbel ULg et al

in Human Genetics (2012), 131

The interest in performing gene-environment interaction studies has seen a significant increase with the increase of advanced molecular genetics techniques. Practically, it became possible to investigate ... [more ▼]

The interest in performing gene-environment interaction studies has seen a significant increase with the increase of advanced molecular genetics techniques. Practically, it became possible to investigate the role of environmental factors in disease risk and hence to investigate their role as genetic effect modifiers. The understanding that genetics is important in the uptake and metabolism of toxic substances is an example of how genetic profiles can modify important environmental risk factors to disease. Several rationales exist to set up gene-environment interaction studies and the technical challenges related to these studies-when the number of environmental or genetic risk factors is relatively small-has been described before. In the post-genomic era, it is now possible to study thousands of genes and their interaction with the environment. This brings along a whole range of new challenges and opportunities. Despite a continuing effort in developing efficient methods and optimal bioinformatics infrastructures to deal with the available wealth of data, the challenge remains how to best present and analyze genome-wide environmental interaction (GWEI) studies involving multiple genetic and environmental factors. Since GWEIs are performed at the intersection of statistical genetics, bioinformatics and epidemiology, usually similar problems need to be dealt with as for genome-wide association gene-gene interaction studies. However, additional complexities need to be considered which are typical for large-scale epidemiological studies, but are also related to "joining" two heterogeneous types of data in explaining complex disease trait variation or for prediction purposes. [less ▲]

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