References of "Van Steen, Kristel"
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See detailPrognostic Value of Serologic and Histologic Markers on Clinical Relapse in Ulcerative Colitis Patients With Mucosal Healing
Bessissow, Talat; Lemmens, Bart; Ferrante, Marc et al

in American Journal of Gastroenterology (2012), 11(107), 1684-92

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See detailActive Foxp3 (+) Regulatory T Cells Rather Than Other Foxp3 (+) T Cells Subsets CorrelateWith Clinical Response To Infliximab Therapy For IBD
Li, Z; Vermeire, S; Bullens, D et al

Poster (2012, October)

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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 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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