References of "Van Steen, Kristel"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailCombined analysis from eleven linkage studies of bipolar disorder provides strong evidence of susceptibility loci on chromosomes 6q and 8q
McQueen, M. B.; Devlin, B.; Faraone, S. V. et al

in American Journal of Human Genetics (2005), 77(4), 582-95

Several independent studies and meta-analyses aimed at identifying genomic regions linked to bipolar disorder (BP) have failed to find clear and consistent evidence of linkage regions. Our hypothesis is ... [more ▼]

Several independent studies and meta-analyses aimed at identifying genomic regions linked to bipolar disorder (BP) have failed to find clear and consistent evidence of linkage regions. Our hypothesis is that combining the original genotype data provides benefits of increased power and control over sources of heterogeneity that outweigh the difficulty and potential pitfalls of the implementation. We conducted a combined analysis using the original genotype data from 11 BP genomewide linkage scans comprising 5,179 individuals from 1,067 families. Heterogeneity among studies was minimized in our analyses by using uniform methods of analysis and a common, standardized marker map and was assessed using novel methods developed for meta-analysis of genome scans. To date, this collaboration is the largest and most comprehensive analysis of linkage samples involving a psychiatric disorder. We demonstrate that combining original genome-scan data is a powerful approach for the elucidation of linkage regions underlying complex disease. Our results establish genomewide significant linkage to BP on chromosomes 6q and 8q, which provides solid information to guide future gene-finding efforts that rely on fine-mapping and association approaches. [less ▲]

Detailed reference viewed: 9 (3 ULg)
Full Text
See detailTesting for association in genetic studies
Laird, N. M.; Kraft, P.; Lange, C. et al

in Silverman, E.; Shapiro, S. D.; Lomas, D. A. (Eds.) et al Respiratory Genetics (2005)

Detailed reference viewed: 2 (2 ULg)
Full Text
Peer Reviewed
See detailCrohn's disease and month of birth.
Van Ranst, Marc; Joossens, Marie; Joossens, Sofie et al

in Inflammatory Bowel Diseases (2005), 11(6), 597-9

BACKGROUND: Environmental factors trigger the onset of inflammatory bowel disease (IBD) in genetically predisposed individuals. Exposure to seasonal external factors during the maturation of the immune ... [more ▼]

BACKGROUND: Environmental factors trigger the onset of inflammatory bowel disease (IBD) in genetically predisposed individuals. Exposure to seasonal external factors during the maturation of the immune system is suspected to be an inducing factor for IBD. Some studies suggested an association between the month of birth and the later development of IBD. We studied this putative relationship in a large cohort of Belgian patients with Crohn's disease (CD). METHODS: Data from 1025 patients born between 1935 and 1990 were collected. Diagnosis of CD was based on generally accepted clinical, endoscopic, and histologic criteria. As a control group, a cohort of 5125 non-IBD patients seen at the same hospital and matched for birth year and sex was used. Odds ratios were calculated using multivariate unconditional logistic regression including the matching variables and allowing for cyclic variation in risk with month of birth. RESULTS: A cyclic pattern described by a 4-month periodic function was observed with peaks in April and August. Moreover, being born in June significantly reduced the risk of developing CD later in life (P = 0.012). CONCLUSION: In this Belgian cohort, a significant association was found between the month of birth and later development of IBD; a significant reduced risk to develop CD was observed for people born in June. Moreover, environmental yearly reoccurring factors during pregnancy or postpartum might be associated with the occurrence of CD later in life. [less ▲]

Detailed reference viewed: 22 (3 ULg)
Full Text
Peer Reviewed
See detailNon-small cell lung cancer and health-related quality of life (HRQOL): Is baseline HRQOL of prognostic value for survival?
Bottomley, A.; Smit, E.; Efficace, F. et al

in Quality of Life Research (2005), 14(9), 20501013

Detailed reference viewed: 8 (2 ULg)
Full Text
Peer Reviewed
See detailGenomic screening in family-based association testing
Murphy, A.; McGueen, M. B.; Su, J. et al

in BMC Genetics (2005), 6

Due to the recent gains in the availability of single-nucleotide polymorphism data, genome-wide association testing has become feasible. It is hoped that this additional data may confirm the presence of ... [more ▼]

Due to the recent gains in the availability of single-nucleotide polymorphism data, genome-wide association testing has become feasible. It is hoped that this additional data may confirm the presence of disease susceptibility loci, and identify new genetic determinants of disease. However, the problem of multiple comparisons threatens to diminish any potential gains from this newly available data. To circumvent the multiple comparisons issue, we utilize a recently developed screening technique using family-based association testing. This screening methodology allows for the identification of the most promising single-nucleotide polymorphisms for testing without biasing the nominal significance level of our test statistic. We compare the results of our screening technique across univariate and multivariate family-based association tests. From our analyses, we observe that the screening technique, applied to different settings, is fairly consistent in identifying optimal markers for testing. One of the identified markers, TSC0047225, was significantly associated with both the ttth1 (p=0.004) and ttth1-ttth4 (p=0.004) phenotype(s). We find that both univariate- and multivariate-based screening techniques are powerful tools for detecting an association. [less ▲]

Detailed reference viewed: 13 (6 ULg)
Full Text
Peer Reviewed
See detailComparison of linkage and association strategies for quantitative traits using the COGA dataset
McQueen, M. B.; Murphy, A.; Kraft, P. et al

in Genetic Epidemiology. Supplement (2005), 29(Suppl I), 1-9

Genome scans using dense single-nucleotide polymorphism ( SNP) data have recently become a reality. It is thought that the increase in information content for linkage analysis as a result of the denser ... [more ▼]

Genome scans using dense single-nucleotide polymorphism ( SNP) data have recently become a reality. It is thought that the increase in information content for linkage analysis as a result of the denser scans will help refine previously identified linkage regions and possibly identify new regions not identifiable using the sparser, microsatellite scans. In the context of the dense SNP scans, it is also possible to consider association strategies to provide even more information about potential regions of interest. To circumvent the multiple-testing issues inherent in association analysis, we use a recently developed strategy, implemented in PBAT, which screens the data to identify the optimal SNPs for testing, without biasing the nominal significance level. We compare the results from the PBAT analysis to that of quantitative linkage analysis on chromosome 4 using the Collaborative Study on the Genetics of Alcoholism data, as released through Genetic Analysis Workshop 14. [less ▲]

Detailed reference viewed: 14 (3 ULg)
Full Text
Peer Reviewed
See detailGenomic screening and replication in one data set in family-based association testing
Lange, C.; Van Steen, Kristel ULg; McQueen, M. et al

in Conference Abstract Book (2005)

Detailed reference viewed: 6 (2 ULg)
Full Text
Peer Reviewed
See detailGenetic predictors of asthma exacerbations among children in the childhood asthma management program
Celedon, J. C.; Van Steen, Kristel ULg; Lange, C. et al

in Conference Abstract Book (2005)

Detailed reference viewed: 7 (2 ULg)
Full Text
Peer Reviewed
See detailBaseline health-related quality-of-life data as prognostic factors in a phase III multicentre study of women with metastatic breast cancer
Efficace, F.; Biganzoli, L.; Piccart, M. et al

in European Journal of Cancer (2004), 40(7), 1021-1030

The potential value of baseline health-related quality-of-life (HRQOL) and clinical factors in predicting prognosis was examined using data from an international randomised phase III trial which compared ... [more ▼]

The potential value of baseline health-related quality-of-life (HRQOL) and clinical factors in predicting prognosis was examined using data from an international randomised phase III trial which compared doxorubicin and paclitaxel with doxorubicin and cylophosphamide as first line chemotherapy in 275 women with metastatic breast cancer. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and the related breast module (QLQ-BR23) were used to assess baseline HRQOL data. The Cox proportional-hazards regression model was used for both univariate and multivariate analyses of survival. In the univariate analyses, performance status (P < 0.001) and number of sites involved (P = 0.001) were the most important clinical prognostic factors. The HRQOL variables at baseline most strongly associated with longer survival were better appetite, physical and role functioning, as well as less fatigue (P < 0.001). The final multivariate model retained performance status (P < 0.001) and appetite loss (P = 0.005) as the variables best predicting survival. Substantial loss of appetite was the only independent HRQOL factor predicting poor survival and was strongly correlated (\r\ > 0.5) with fatigue, role and physical functioning. In addition to known clinical factors, appetite loss appears to be a significant prognostic factor for survival in women with metastatic breast cancer. However, the mechanism underlying this association remains to be precisely defined in future studies. (C) 2004 Elsevier Ltd. All rights reserved. [less ▲]

Detailed reference viewed: 10 (2 ULg)
Full Text
Peer Reviewed
See detailIntroducing the multivariate dale model in population-based genetic association studies
Van Steen, Kristel ULg; Tahri, N.; Molenberghs, G.

in Biometrical Journal = Biometrische Zeitschrift (2004), 46(2), 187-202

Until recently, the most common parametric approaches to study the combined effects of several genetic polymorphisms located within a gene or in a small genomic region are, at the genotype level, logistic ... [more ▼]

Until recently, the most common parametric approaches to study the combined effects of several genetic polymorphisms located within a gene or in a small genomic region are, at the genotype level, logistic regressions and at the haplotype level, haplotype analyses. An alternative modeling approach, based on the case/control principle, is to regard exposures (e.g., genetic data such as derived from Single Nucleotide Polymorphisms - SNPs) as random and disease status as fixed and to use a marginal multivariate model that accounts for inter-relationships between exposures. One such model is the multivariate Dale model. This model is based on multiple logistic regressions. That is why the model, applied in a case/control setting, leads to straightforward interpretations that are similar to those drawn in a classical logistic modeling framework. [less ▲]

Detailed reference viewed: 15 (2 ULg)
Full Text
Peer Reviewed
See detailPancreatic autoantibodies in inflammatory bowel disease
Joossens, S.; Vermeire, S.; Van Steen, Kristel ULg et al

in Inflammatory Bowel Diseases (2004), 10(6), 771-777

Background: Autoantibodies against exocrine pancreas (PABs) have been reported to be specific for Crohn's disease (CD), albeit at a low prevalence (30%). We studied PABs in patients with inflammatory ... [more ▼]

Background: Autoantibodies against exocrine pancreas (PABs) have been reported to be specific for Crohn's disease (CD), albeit at a low prevalence (30%). We studied PABs in patients with inflammatory bowel disease (IBD), unaffected family members, and control subjects. Methods: A Belgian study cohort of 575 subjects, including 289 IBD patients (CD, 169 patients; ulcerative colitis [UC], 120 patients), 108 unaffected first-degree relatives, 78 subjects with non-IBD gastrointestinal disorders (gastrointestinal control subjects [GIcos]), and 100 healthy control subjects (Hcos), were tested for PAB by a standardized indirect immunofluorescence method. Results: The prevalence of PABs in this study cohort was 32% for CD, 23.3% for UC, and 22.2% for their unaffected family members (all P < 0.001), compared with 1.3% for GIcos and 0% for Hcos. Two staining patterns could be observed: an intracellular pattern (IC); and an extracellular pattern (EC). The EC was significantly more prevalent in CD patients compared with UC patients (P = 0.014), and higher titers of this pattern were found in CD patients (P = 0.01). Both PAB patterns were negatively associated with stricturing disease behavior of CD (P = 0.021). The IC was associated with familial CD (P = 0.0009) and familial UC (P = 0.0003). Conclusions: The prevalence of PAB found in CD patients in this study was similar to that cited in previous reports. In contrast to these reports, we also found an increased prevalence of PABs in patients with UC and in unaffected first-degree relatives of IBD patients. We observed two main staining patterns, both of which were present in IBD and were associated with specific phenotypes of the disease. [less ▲]

Detailed reference viewed: 10 (4 ULg)
Full Text
Peer Reviewed
See detailTumour necrosis factor- receptor 1 and 2 polymorhpisms in inflammatory bowel disease and their association with response to infliximab
Pierik, M.; Vermeire, S.; Van Steen, Kristel ULg et al

in Alimentary Pharmacology & Therapeutics (2004), 20

Detailed reference viewed: 6 (2 ULg)
Full Text
Peer Reviewed
See detailHealth-related quality of life parameters as prognostic factors in a nonmetastatic breast cancer population: An international multicenter study
Efficace, F.; Therasse, P.; Piccart, M. J. et al

in Journal of Clinical Oncology (2004), 22(16), 3381-3388

Purpose The purpose of this research was to evaluate whether baseline health-related quality of life (HRQOL) parameters are prognostic factors for survival in locally advanced breast cancer patients ... [more ▼]

Purpose The purpose of this research was to evaluate whether baseline health-related quality of life (HRQOL) parameters are prognostic factors for survival in locally advanced breast cancer patients. Although the literature highlights the important role of HRQOL parameters in predicting survival in advanced metastatic disease, little evidence exists for earlier stages. Patients and Methods The overall sample consisted of 448 patients randomly assigned to receive cyclophosphamide, epirubicin, and fluorouracil versus epirubicin, cyclophosphamide, and granulocyte colony-stimulating factor. Patients were enrolled in 12 countries. HRQOL baseline scores were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30. The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap resampling technique was used to assess the stability of the outcomes. Bootstrap results were then applied for model averaging purposes as a means to account for the observed model selection uncertainty. Results The final multivariate model retained inflammatory breast cancer (T4d) as the only factor predicting overall survival (OS) with a hazard ratio of 1.375 (95% CI, 1.027 to 1.840; P = .03). The presence of inflammatory breast cancer lowers the median survival time from 6.6 to 4.2 years (36% reduction). None of the preselected HRQOL variables were prognostic for OS or disease-free survival, in either the univariate or multivariate analysis. Conclusion Our findings suggest that baseline HBQOL parameters have no prognostic value in a nonmetastatic breast cancer population. [less ▲]

Detailed reference viewed: 12 (3 ULg)
Full Text
Peer Reviewed
See detailGenome wide scan in a Flemish inflammatory bowel disease population: support for the IBD4 locus, population heterogeneity, and epistasis
Vermeire, S.; Rutgeerts, P.; Van Steen, Kristel ULg et al

in Gut (2004), 53(7), 980-986

Background and aims: Genome wide scans in inflammatory bowel disease (IBD) have indicated various susceptibility regions with replication of 16cen (IBD1), 12q (IBD2), 6p (IBD3), 14q11 (IBD4), and 3p21. As ... [more ▼]

Background and aims: Genome wide scans in inflammatory bowel disease (IBD) have indicated various susceptibility regions with replication of 16cen (IBD1), 12q (IBD2), 6p (IBD3), 14q11 (IBD4), and 3p21. As no linkage was previously found on IBD regions 3, 7, 12, and 16 in Flemish IBD families, a genome wide scan was performed to detect other susceptibility regions in this population. Methods: A cohort of 149 IBD affected relative pairs, all recruited from the Northern Flemish part of Belgium, were genotyped using microsatellite markers at 12 cM intervals, and analysed by Genehunter non-parametric linkage software. All families were further genotyped for the three main Crohn's disease associated variants in the NOD2/CARD15 gene. Results: Nominal evidence for linkage was observed on chromosomes 1 (D1S197: multipoint nonparametric linkage (NPL) score 2.57, p = 0.004; and at D1S305-D1S252: NPL 2.97, p = 0.001), 4q (D4S406: NPL 1.95, p = 0.03), 6q16 (D6S314: NPL 2.44, p = 0.007), 10p12 (D10S197: NPL 2.05, p = 0.02), 11q22 (D11S35-D11S927: NPL 1.95, p = 0.02) 14q11-12 (D14S80: NPL 2.41, p = 0.008), 20p12 (D20S192: NPL 2.7, p = 0.003), and Xq (DXS990: NPL 1.70, p = 0.04). A total of 51.4% of patients carried at least one NOD2/CARD15 variant. Furthermore, epistasis was observed between susceptibility regions 6q/10p and 20p/10p. Conclusion: Genome scanning in a Flemish IBD population found nominal evidence for linkage on 1p, 4q, 10p12, and 14q11, overlapping with other genome scan results, with linkage on 14q11-12 supporting the IBD4 locus. The results further show that epistasis is contributing to the complex model of IBD and indicate that population heterogeneity is not to be underestimated. Finally, NOD2/CARD15 is clearly implicated in the Flemish IBD population. [less ▲]

Detailed reference viewed: 17 (3 ULg)
Full Text
See detailMulticollinearity
Van Steen, Kristel ULg; Molenberghs, G.

in Chow, Shein-Chung (Ed.) Encyclopedia of Biopharmaceutical Statistics (2004)

Detailed reference viewed: 15 (6 ULg)
Full Text
Peer Reviewed
See detailA family-based association test for repeatedly measured quantitative traits adjusting for unknown environmental and/or polygenic effects
Lange, C.; Van Steen, Kristel ULg; Andrew, T. et al

in Statistical Applications in Genetics and Molecular Biology (2004), 3(1), 17

Detailed reference viewed: 12 (2 ULg)
Full Text
Peer Reviewed
See detailDeficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn's disease and ulcerative colitis
Franchimont, D.; Vermeire, S.; El Housni, H. et al

in Gut (2004), 53(7), 987-992

Background and aims: Elicitation of an innate immune response to bacterial products is mediated through pattern recognition receptors (PRRs) such as the toll-like receptors (TLRs) and the NODs. The ... [more ▼]

Background and aims: Elicitation of an innate immune response to bacterial products is mediated through pattern recognition receptors (PRRs) such as the toll-like receptors (TLRs) and the NODs. The recently characterised Asp299Gly polymorphism in the lipopolysaccharide (LPS) receptor TLR4 is associated with impaired LPS signalling and increased susceptibility to Gram negative infections. We sought to determine whether this polymorphism was associated with Crohn's disease ( CD) and/or ulcerative colitis (UC). Methods: Allele frequencies of the TLR4 Asp299Gly polymorphism and the three NOD2/CARD15 polymorphisms (Arg702Trp, Gly908Arg, and Leu1007fsinsC) were assessed in two independent cohorts of CD patients ( cohort 1, n = 334; cohort 2, n = 114), in 163 UC patients, and in 140 controls. A transmission disequilibrium test (TDT) was then performed on 318 inflammatory bowel disease (IBD) trios. Results: The allele frequency of the TLR4 Asp299Gly polymorphism was significantly higher in CD ( cohort 1: 11% v 5%, odds ratio ( OR) 2.31 (95% confidence interval (CI) 1.28 - 4.17), p = 0.004; and cohort 2: 12% v 5%, OR 2.45 ( 95% CI 1.24 - 4.81), p = 0.007) and UC patients (10% v 5%, OR 2.05 ( 95% CI 1.07 3.93), p = 0.027) compared with the control population. A TDT on 318 IBD trios demonstrated preferential transmission of the TLR4 Asp299Gly polymorphism from heterozygous parents to affected children (T/U: 68/34, p = 0.01). Carrying polymorphisms in both TLR4 and NOD2 was associated with a genotype relative risk (RR) of 4.7 compared with a RR of 2.6 and 2.5 for TLR4 and NOD2 variants separately. Conclusion: We have reported on a novel association of the TLR4 Asp299Gly polymorphism with both CD and UC. This finding further supports the genetic influence of PRRs in triggering IBD. [less ▲]

Detailed reference viewed: 15 (3 ULg)
Full Text
Peer Reviewed
See detailTransmission of CARD15 (NOD2) variants within families of patients with inflammatory bowel disease.
Esters, Nele; Pierik, Marie; Van Steen, Kristel ULg et al

in American Journal of Gastroenterology (2004), 99(2), 299-305

OBJECTIVES: Three single nucleotide polymorphisms (SNPs) in CARD15 have been independently associated with Crohn's disease (CD). Since nothing is known about the transmission of these variants within ... [more ▼]

OBJECTIVES: Three single nucleotide polymorphisms (SNPs) in CARD15 have been independently associated with Crohn's disease (CD). Since nothing is known about the transmission of these variants within families, this was the subject of our study in Flemish patients with inflammatory bowel disease (IBD) and their healthy relatives. METHODS: A cohort of 1,670 individuals (570 CD, 173 UC, 165 healthy controls, 762 first-degree unaffected relatives of CD patients) was genotyped for Arg702Trp, Gly908Arg, and Leu1007fsinsC. Mutant allele and carrier frequencies were compared between groups. Segregation patterns were compared using a bivariate Dale model. RESULTS: The carrier prevalence of CARD15 variants for CD patients was 46.3%, compared to 20.6% for healthy controls and 22.0% for ulcerative colitis (UC) patients (both p < 0.0001). An increased carriage rate of CARD15 variants was observed in unaffected relatives of CD patients (37.3%; p < 0.0001 vs controls), although this was significantly lower than in the CD patients (p = 0.001). Paternal transmission gave a 5.17-fold higher chance for the child to develop the disease compared to maternal transmission (95% CI [1.59, 16.78]; p = 0.0063). UC patients belonging to mixed IBD families carried significantly more mutations (42.3%) compared to other UC patients (18.4%) (p < 0.01). CONCLUSIONS: Maternal transmission of the CARD15 variant allele is associated with a lower proportion of affected individuals compared to paternal transmission. Therefore, maternal transmission does not carry an increased risk of transmission as does paternal transmission. The increased mutation carriage in unaffected siblings of CD patients and in UC patients belonging to mixed families suggests that other factors than CARD15 contribute to the eventual disease expression. [less ▲]

Detailed reference viewed: 8 (2 ULg)
Full Text
Peer Reviewed
See detailInterassay and interobserver variability in the detection of anti-neutrophil cytoplasmic antibodies in patients with ulcerative colitis.
Joossens, Sofie; Daperno, Marco; Shums, Zakera et al

in Clinical Chemistry (2004), 50(8), 1422-5

Detailed reference viewed: 13 (3 ULg)