References of "Van Steen, Kristel"
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See detailGenetic variation in the autophagy gene ULK1 and risk of Crohn's disease
Henckaerts, Liesbeth; Cleynen, Isabelle; Brinar, Marko et al

in Inflammatory Bowel Diseases (2011), 17(6), 1392-1397

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See detailModel-Based Multifactor Dimensionality Reduction for detecting epistasis in case-control data in the presence of noise
Cattaert, Tom ULg; Calle, Luz M; Dudek, Scott T et al

in Annals of Human Genetics (2011), 75(1), 78-89

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See detailLong term evolution and impact of immunomodulator cotreatment and withdrawal on infliximab on trough levels in 223 patients with Crohn's disease
Drobne, D; Bossuyt, P; Breynaert, C et al

in Journal of Crohn’s and Colitis [=JCC] (2011)

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See detailThe protease genes CYLD and USP40 are associated with Crohn's disease: results from a European Consortium
Cleynen, I; Artieda, M; Szczyoiorska, M et al

in Gastroenterology (2011), 140(5), 269

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See detailAnti-TNF induced skin manifestations in IBD patients: characterization and search for predisposing factors
Cleynen, I; Van Moerkercke, W; Vande Casteele, N et al

in Acta Gastro-Enterologica Belgica (2011), 74

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See detailProfile of Belgian Pediatric Crohn's Disease Patients: Associations between variables at diagnosis
De Greef, E; Hoffman, I; Smets, F et al

in Gastroenterology (2011), 140(5), 787

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See detailProfile of Belgian Pediatric Crohn's Disease Patients: Associations between variables at diagnosis
De Greef, E; Hoffman, I; Smets, F et al

in Acta Gastro-Enterologica Belgica (2011), 74

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See detailProfile of Belgian Pediatric Crohn's Disease Patients: Associations between variables at diagnosis
De Greef, E; Hoffman, I; Smets, F et al

in Journal of Crohn’s and Colitis [=JCC] (2011), 5(1), 156

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See detailProfile of Belgian Pediatric Crohn's Disease Patients: Presentation and diagnostic features
De Greef, E; Hoffman, I; Smets, F et al

in Gastroenterology (2011), 140(5), 786

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See detailProfile of Belgian Pediatric Crohn's Disease Patients: Presentation and diagnostic features
De Greef, E; Hoffman, I; Smets, F et al

in Acta Gastro-Enterologica Belgica (2011), 74

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See detailProfile of Belgian Pediatric Crohn's Disease Patients: Presentation and diagnostic features
De Greef, E; Hoffman, I; Smets, F et al

in Journal of Crohn’s and Colitis [=JCC] (2011), 5(1), 155

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See detailPerspectives on genome-wide multi-stage family-based association studies.
Van Steen, Kristel ULg

in Statistics in Medicine (2011), 30(18), 2201-2221

With the establishment of large consortiums of researchers, genome-wide association (GWA) studies have become increasingly popular and feasible. Although most of these association studies focus on ... [more ▼]

With the establishment of large consortiums of researchers, genome-wide association (GWA) studies have become increasingly popular and feasible. Although most of these association studies focus on unrelated individuals, a lot of advantages can be exploited by including families in the analysis as well. To overcome the additional genotyping cost, multi-stage designs are particularly useful. In this article, I offer a perspective view on genome-wide family-based association analyses, both within a model-based and model-free paradigm. I highlight how multi-stage designs and analysis techniques, which are quite popular in clinical epidemiology, can enter GWA settings. I furthermore discuss how they have proven successful in reducing analysis complexity, and in overcoming one of the most cumbersome statistical hurdles in the genome-wide context, namely controlling increased false positives due to multiple testing. [less ▲]

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See detailOutcome of pregnancy in women with inflammatory bowel disease treated with antitumor necrosis factor therapy.
Schnitzler, François ULg; Fidder, Herma; Boukerroucha, Meriem ULg et al

in Inflammatory Bowel Diseases (2011), 17(9), 1846-1854

BACKGROUND:: Infliximab (IFX) and adalimumab (ADA) are attractive treatment options in patients with inflammatory bowel disease (IBD) also during pregnancy but there is still limited data on the benefit ... [more ▼]

BACKGROUND:: Infliximab (IFX) and adalimumab (ADA) are attractive treatment options in patients with inflammatory bowel disease (IBD) also during pregnancy but there is still limited data on the benefit/risk profile of IFX and ADA during pregnancy. METHODS:: This observational study assessed pregnancy outcomes in 212 women with IBD under antitumor necrosis factor alpha (TNF) treatment at our IBD unit. Pregnancy outcomes in 42 pregnancies with direct exposure to anti-TNF treatment (35 IFX, 7 ADA) were compared with that in 23 pregnancies prior to IBD diagnosis, 78 pregnancies before start of IFX, 53 pregnancies with indirect exposure to IFX, and 56 matched pregnancies in healthy women. RESULTS:: Thirty-two of the 42 pregnancies ended in live births with a median gestational age of 38 weeks (interquartile range [IQR] 37-39). There were seven premature deliveries, six children had low birth weight, and there was one stillbirth. One boy weighed 1640 g delivered at week 33, died at age of 13 days because of necrotizing enterocolitis. A total of eight abortions (one patient wish) occurred in seven women. Trisomy 18 was diagnosed in one fetus of a mother with CD at age 37 under ADA treatment (40 mg weekly) and pregnancy was terminated. Pregnancy outcomes after direct exposure to anti-TNF treatment were not different from those in pregnancies before anti-TNF treatment or with indirect exposure to anti-TNF treatment but outcomes were worse than in pregnancies before IBD diagnosis. CONCLUSIONS:: Direct exposure to anti-TNF treatment during pregnancy was not related to a higher incidence of adverse pregnancy outcomes than IBD overall. (Inflamm Bowel Dis 2011;). [less ▲]

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See detailEffects of haptoglobin polymorphisms and deficiency on susceptibility to inflammatory bowel disease and on severity of murine colitis.
Marquez, L.; Shen, C.; Cleynen, I. et al

in Gut (2011), 61(4), 528-534

BackgroundHaptoglobin (Hp) is a haemoglobin-binding protein with immunomodulatory properties. Its gene (16q22) harbours a common polymorphism with two different alleles: Hp1 and Hp2. Genotype Hp22 has ... [more ▼]

BackgroundHaptoglobin (Hp) is a haemoglobin-binding protein with immunomodulatory properties. Its gene (16q22) harbours a common polymorphism with two different alleles: Hp1 and Hp2. Genotype Hp22 has been shown to be over-represented in different immune diseases. Results in Crohn's disease (CD) are contradictory.AimsTo determine whether Hp plays a role in inflammatory bowel disease, both genetically and functionally.Methods1061 patients with CD, 755 with ulcerative colitis (UC) and 152 with primary sclerosing cholangitis, as well as 452 healthy controls, were genotyped using touch-down PCR. To confirm association results, 464 CD trios and 151 UC trios were genotyped. Serum Hp concentrations were determined in 62 individuals of different genotype. Colitis was induced in mice with dextran sulphate sodium (DSS) and oxazolone (Oxa). Cytokine production was evaluated by mRNA quantification in colonic tissue and ELISA on supernatants of mesenteric lymph node cells.ResultsPrevalence of Hp2 was higher in CD and UC than in controls. In the confirmatory cohorts, Hp2 was over-transmitted to the affected offspring. Serum Hp concentrations were higher in individuals with genotypes Hp11 and Hp21 than in those with Hp22 (1.38 vs 0.89 g/l). DSS- and Oxa-induced colitis were more severe in Hp-deficient mice than in control mice and accompanied by higher concentrations (although not statistically significantly different) of tissue mRNA for cytokines. Interleukin-17 production was significantly higher in the presence of Hp-deficient serum compared with wild-type serum.ConclusionsThe Hp gene may play a role in susceptibility to inflammatory bowel disease. Its implication in other immune diseases underscores the common pathways between these diseases. Experimental models of colitis showed that Hp has a protective role in inflammatory colitis, most likely by inhibiting the production of Th1 and Th17 cytokines. [less ▲]

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See detailModel-Based Multifactor Dimensionality Reduction to detect epistasis for quantitative traits in the presence of error-free and noisy data.
Mahachie John, Jestinah ULg; Van Lishout, François ULg; Van Steen, Kristel ULg

in European Journal of Human Genetics (2011), 19

Detecting gene-gene interactions or epistasis in studies of human complex diseases is a big challenge in the area of epidemiology. To address this problem, several methods have been developed, mainly in ... [more ▼]

Detecting gene-gene interactions or epistasis in studies of human complex diseases is a big challenge in the area of epidemiology. To address this problem, several methods have been developed, mainly in the context of data dimensionality reduction. One of these methods, Model-Based Multifactor Dimensionality Reduction, has so far mainly been applied to case-control studies. In this study, we evaluate the power of Model-Based Multifactor Dimensionality Reduction for quantitative traits to detect gene-gene interactions (epistasis) in the presence of error-free and noisy data. Considered sources of error are genotyping errors, missing genotypes, phenotypic mixtures and genetic heterogeneity. Our simulation study encompasses a variety of settings with varying minor allele frequencies and genetic variance for different epistasis models. On each simulated data, we have performed Model-Based Multifactor Dimensionality Reduction in two ways: with and without adjustment for main effects of (known) functional SNPs. In line with binary trait counterparts, our simulations show that the power is lowest in the presence of phenotypic mixtures or genetic heterogeneity compared to scenarios with missing genotypes or genotyping errors. In addition, empirical power estimates reduce even further with main effects corrections, but at the same time, false-positive percentages are reduced as well. In conclusion, phenotypic mixtures and genetic heterogeneity remain challenging for epistasis detection, and careful thought must be given to the way important lower-order effects are accounted for in the analysis.European Journal of Human Genetics advance online publication, 16 March 2011; doi:10.1038/ejhg.2011.17. [less ▲]

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See detailMucosal gene expression profiling differentiates early from late ileal Crohn's disease
Arijs, I; Van Lommel, L; De Hertogh, G et al

in Acta Gastro-Enterologica Belgica (2011)

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See detailTolerability of shortened infliximab infusion times in patients with inflammatory bowel diseases: a single-center cohort study.
Breynaert, Christine; Ferrante, Marc; Fidder, Herma et al

in American Journal of Gastroenterology (2011), 106(4), 778-85

OBJECTIVES: Scheduled maintenance therapy with infliximab decreases the risk of infusion reactions. Many centers have accelerated infusion times to 1 h in selected patients who tolerate 5 mg/kg infliximab ... [more ▼]

OBJECTIVES: Scheduled maintenance therapy with infliximab decreases the risk of infusion reactions. Many centers have accelerated infusion times to 1 h in selected patients who tolerate 5 mg/kg infliximab infusions. The aim of this study was to compare the tolerability of 1-h and 2-h infliximab infusions in patients with inflammatory bowel disease (IBD) in a large single-center cohort. The primary end point was the incidence of infusion reactions in both groups. METHODS: A retrospective chart analysis of all IBD patients treated with infliximab was performed. Infusions in scheduled maintenance for at least 6 months from December 1994 until March 2009 were included. All patients were treated at the infusion unit or during hospitalization under standard operating procedures. Infusion parameters were prospectively recorded. From 2004, in patients tolerating at least four 2-h infusions, infusions were given over 1 h. RESULTS: As of March 2009, 953 patients with IBD (77.6% Crohn's disease, 22.4% ulcerative colitis) had been treated with infliximab. A total of 474 patients met the criteria of scheduled maintenance therapy. In total, 9,155 maintenance infusions were administered (4,307 over 1 h). No severe infusion reactions were documented. Mild acute reactions occurred in 0.6% (27/4,307) of the 1-h-infusion group and in 1.7% (80/4848) of the 2-h infusion group (P=0.0034). Delayed infusion reactions occurred in 0.2% of 1-h and 0.5% of 2-h infusion group patients (P=0.277). Loss of tolerability due to infusion reactions (1-h group 2.9% versus 2-h group 4.1%) was evenly distributed (P=0.34). None of the prespecified variables were predictive of infusion reactions in a multivariate analysis. CONCLUSIONS: In patients with IBD tolerating 2-h infusions of infliximab scheduled maintenance therapy, the infusion time can be shortened to 1 h with good tolerability. No severe reactions were observed and no predictors of infusion reactions were identified. [less ▲]

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See detailHigh-throughput method for comparative analysis of denaturing gradient gel electrophoresis profiles from human fecal samples reveals significant increases in two bifidobacterial species after inulin-type prebiotic intake.
Joossens, Marie; Huys, Geert; Van Steen, Kristel ULg et al

in FEMS Microbiology Ecology (2011), 75(2), 343-9

Denaturing gradient gel electrophoresis (DGGE) is one of the most commonly used molecular tools to study complex microbial communities. Despite its widespread use, meaningful interpretative analysis ... [more ▼]

Denaturing gradient gel electrophoresis (DGGE) is one of the most commonly used molecular tools to study complex microbial communities. Despite its widespread use, meaningful interpretative analysis remains a major drawback of this method. We evaluated the combination of computer-assisted band-matching with nonparametric statistics for comparative analysis of DGGE banding patterns. Fecal samples from 17 healthy volunteers who consumed 20 g of the prebiotic compound oligofructose-enriched inulin (OF-IN) for 4 weeks were analyzed before and after treatment. DGGE fingerprinting profiles were analyzed using bionumerics software version 4.6., which resulted in a data matrix that was used for statistical analysis. When comparing DGGE profiles before and after OF-IN intake with a Wilcoxon nonparametric test for paired data, two band-classes increased significantly after OF-IN intake (P<0.003 and <0.02). These two band-classes could be assigned to the species Bifidobacterium longum and Bifidobacterium adolescentis by band-sequencing analysis, and their significant increase was quantitatively confirmed with real-time PCR using species-specific primers (respectively P<0.012 and <0.010). Therefore, the nonparametric analysis of a data matrix obtained by computer-assisted band-matching of complex profiles facilitated the interpretative analysis of these profiles and provided an objective and high-throughput method for the detection of significant taxonomic differences in larger numbers of complex profiles. [less ▲]

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See detailSequencing of DISC1 pathway genes reveals increased burden of rare missense variants in schizophrenia patients from a northern Swedish population.
Moens, Lotte N.; De Rijk, Peter; Reumers, Joke et al

in PloS one (2011), 6(8), 23450

In recent years, DISC1 has emerged as one of the most credible and best supported candidate genes for schizophrenia and related neuropsychiatric disorders. Furthermore, increasing evidence--both genetic ... [more ▼]

In recent years, DISC1 has emerged as one of the most credible and best supported candidate genes for schizophrenia and related neuropsychiatric disorders. Furthermore, increasing evidence--both genetic and functional--indicates that many of its protein interaction partners are also involved in the development of these diseases. In this study, we applied a pooled sample 454 sequencing strategy, to explore the contribution of genetic variation in DISC1 and 10 of its interaction partners (ATF5, Grb2, FEZ1, LIS-1, PDE4B, NDE1, NDEL1, TRAF3IP1, YWHAE, and ZNF365) to schizophrenia susceptibility in an isolated northern Swedish population. Mutation burden analysis of the identified variants in a population of 486 SZ patients and 514 control individuals, revealed that non-synonymous rare variants with a MAF<0.01 were significantly more present in patients compared to controls (8.64% versus 4.7%, P = 0.018), providing further evidence for the involvement of DISC1 and some of its interaction partners in psychiatric disorders. This increased burden of rare missense variants was even more striking in a subgroup of early onset patients (12.9% versus 4.7%, P = 0.0004), highlighting the importance of studying subgroups of patients and identifying endophenotypes. Upon investigation of the potential functional effects associated with the identified missense variants, we found that approximately 90% of these variants reside in intrinsically disordered protein regions. The observed increase in mutation burden in patients provides further support for the role of the DISC1 pathway in schizophrenia. Furthermore, this study presents the first evidence supporting the involvement of mutations within intrinsically disordered protein regions in the pathogenesis of psychiatric disorders. As many important biological functions depend directly on the disordered state, alteration of this disorder in key pathways may represent an intriguing new disease mechanism for schizophrenia and related neuropsychiatric diseases. Further research into this unexplored domain will be required to elucidate the role of the identified variants in schizophrenia etiology. [less ▲]

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See detailA report of the first biennial meeting on Capita Selecta in Complex Disease Analysis (CSCDA2010), Leuven, Belgium, August 25-27, 2010.
Van Steen, Kristel ULg; Sleegers, Kristel

in Annals of Human Genetics (2011), 75(4), 554-7

There is a need for interdisciplinary assessments and interpretations of -omics underpinnings of human complex diseases. However, often investigators from different, yet overlapping, disciplines ... [more ▼]

There is a need for interdisciplinary assessments and interpretations of -omics underpinnings of human complex diseases. However, often investigators from different, yet overlapping, disciplines experience difficulties in understanding the other discipline's language and there is a clear need for establishing a platform that nourishes interdisciplinary team processes and allows tearing down the professional's tower of Babel. To accommodate these needs, the biennial mini-conference Capita Selecta in Complex Disease Analysis was instigated. Abstracts are freely available online [http://www.aimontefiore.org/cscda2010/]. [less ▲]

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