References of "Van Steen, Kristel"
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See detailPBAT: a comprehensive software package for genome-wide association analysis of complex family-based studies
Van Steen, Kristel ULg; Lange, C.

in Human Genomics (2005), 2(1), 67-9

The PBAT software package (v2.5) provides a unique set of tools for complex family-based association analysis at a genome-wide level. PBAT can handle nuclear families with missing parental genotypes ... [more ▼]

The PBAT software package (v2.5) provides a unique set of tools for complex family-based association analysis at a genome-wide level. PBAT can handle nuclear families with missing parental genotypes, extended pedigrees with missing genotypic information, analysis of single nucleotide polymorphisms (SNPs), haplotype analysis, quantitative traits, multivariate/longitudinal data and time to onset phenotypes. The data analysis can be adjusted for covariates and gene/environment interactions. Haplotype-based features include sliding windows and the reconstruction of the haplotypes of the probands. PBAT's screening tools allow the user successfully to handle the multiple comparisons problem at a genome-wide level, even for 100,000 SNPs and more. Moreover, PBAT is computationally fast. A genome scan of 300,000 SNPs in 2,000 trios takes 4 central processing unit (CPU)-days. PBAT is available for Linux, Sun Solaris and Windows XP. [less ▲]

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See detailGenomic screening in family-based association testing
Murphy, A.; McGueen, M. B.; Su, J. et al

in Genetic Epidemiology. Supplement (2005), 29

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 ▲]

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See detailThe prognostic value of health related quality of life in colorectal cancer patients: A multivariate analysis using a bootstrap model-averaging approach
Efficace, F.; Bottomley, A.; Coens, C. et al

in Quality of Life Research (2005), 14(9), 21371030

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See detailPredicting survival using health related quality of life scores in glioblastoma cancers: Findings from an international phase III randomised controlled trial.
Bottomley, A.; Taphoorn, M.; Coens, C. et al

in Journal of Clinical Oncology (2005), 23(16S), 9601

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See detailAnalysis of incomplete data
Molenberghs, G.; Beunkens, C.; Jansen, I. et al

in 'SAS System for Clinical Trials II (2005)

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See detailGenomic screening and replication using the same data set in family-based association testing
Van Steen, Kristel ULg; McQueen, M. B.; Herbert, A. et al

in Nature Genetics (2005), 37(7), 683-691

The Human Genome Project and its spin- offs are making it increasingly feasible to determine the genetic basis of complex traits using genome- wide association studies. The statistical challenge of ... [more ▼]

The Human Genome Project and its spin- offs are making it increasingly feasible to determine the genetic basis of complex traits using genome- wide association studies. The statistical challenge of analyzing such studies stems from the severe multiple-comparison problem resulting from the analysis of thousands of SNPs. Our methodology for genome- wide family- based association studies, using single SNPs or haplotypes, can identify associations that achieve genome- wide significance. In relation to developing guidelines for our screening tools, we determined lower bounds for the estimated power to detect the gene underlying the disease- susceptibility locus, which hold regardless of the linkage disequilibrium structure present in the data. We also assessed the power of our approach in the presence of multiple disease- susceptibility loci. Our screening tools accommodate genomic control and use the concept of haplotype- tagging SNPs. Our methods use the entire sample and do not require separate screening and validation samples to establish genome- wide significance, as population- based designs do. [less ▲]

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See detailComparison of linkage and association strategies for quantitative traits using the COGA dataset.
McQueen, M. B.; Murphy, A.; Kraft, P. et al

in BMC Genetics (2005), 6 Suppl 1

ABSTRACT : 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 ... [more ▼]

ABSTRACT : 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 ▲]

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See detailAn equivalence test for comparing DNA sequences
Van Steen, Kristel ULg; Raby, B.; Molenberghs, G. et al

in Pharmaceutical Statistics (2005), 4(3), 203-214

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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 ▲]

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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)

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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 ▲]

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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

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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 ▲]

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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 ▲]

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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)

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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)

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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 ▲]

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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 ▲]

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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 ▲]

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