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Molecular reclassification of Crohn's disease by cluster analysis of genetic variants

(2010) PLOS ONE. 5(9).
Author
Organization
Abstract
Background: Crohn's Disease (CD) has a heterogeneous presentation, and is typically classified according to extent and location of disease. The genetic susceptibility to CD is well known and genome-wide association scans (GWAS) and meta-analysis thereof have identified over 30 susceptibility loci. Except for the association between ileal CD and NOD2 mutations, efforts in trying to link CD genetics to clinical subphenotypes have not been very successful. We hypothesized that the large number of confirmed genetic variants enables (better) classification of CD patients. Methodology/Principal Findings: To look for genetic-based subgroups, genotyping results of 46 SNPs identified from CD GWAS were analyzed by Latent Class Analysis (LCA) in CD patients and in healthy controls. Six genetic-based subgroups were identified in CD patients, which were significantly different from the five subgroups found in healthy controls. The identified CD-specific clusters are therefore likely to contribute to disease behavior. We then looked at whether we could relate the genetic-based subgroups to the currently used clinical parameters. Although modest differences in prevalence of disease location and behavior could be observed among the CD clusters, Random Forest analysis showed that patients could not be allocated to one of the 6 genetic-based subgroups based on the typically used clinical parameters alone. This points to a poor relationship between the genetic-based subgroups and the used clinical subphenotypes. Conclusions/Significance: This approach serves as a first step to reclassify Crohn's disease. The used technique can be applied to other common
Keywords
INFLAMMATORY-BOWEL-DISEASE, GENOME-WIDE ASSOCIATION, SUSCEPTIBILITY LOCI, CLASSIFICATION, AUTOPHAGY, GENOTYPE, COHORT, RISK

Citation

Please use this url to cite or link to this publication:

MLA
Cleynen, Isabemme, et al. “Molecular Reclassification of Crohn’s Disease by Cluster Analysis of Genetic Variants.” PLOS ONE, vol. 5, no. 9, 2010.
APA
Cleynen, I., John, J. M. M., Henckaerts, L., Van Moerkercke, W., Rutgeerts, P., Van Steen, K., & Vermeire, S. (2010). Molecular reclassification of Crohn’s disease by cluster analysis of genetic variants. PLOS ONE, 5(9).
Chicago author-date
Cleynen, Isabemme, Jestinah M Mahachie John, Liesbet Henckaerts, Wouter Van Moerkercke, Paul Rutgeerts, Kristel Van Steen, and Severine Vermeire. 2010. “Molecular Reclassification of Crohn’s Disease by Cluster Analysis of Genetic Variants.” PLOS ONE 5 (9).
Chicago author-date (all authors)
Cleynen, Isabemme, Jestinah M Mahachie John, Liesbet Henckaerts, Wouter Van Moerkercke, Paul Rutgeerts, Kristel Van Steen, and Severine Vermeire. 2010. “Molecular Reclassification of Crohn’s Disease by Cluster Analysis of Genetic Variants.” PLOS ONE 5 (9).
Vancouver
1.
Cleynen I, John JMM, Henckaerts L, Van Moerkercke W, Rutgeerts P, Van Steen K, et al. Molecular reclassification of Crohn’s disease by cluster analysis of genetic variants. PLOS ONE. 2010;5(9).
IEEE
[1]
I. Cleynen et al., “Molecular reclassification of Crohn’s disease by cluster analysis of genetic variants,” PLOS ONE, vol. 5, no. 9, 2010.
@article{5906945,
  abstract     = {Background: Crohn's Disease (CD) has a heterogeneous presentation, and is typically classified according to extent and location of disease. The genetic susceptibility to CD is well known and genome-wide association scans (GWAS) and meta-analysis thereof have identified over 30 susceptibility loci. Except for the association between ileal CD and NOD2 mutations, efforts in trying to link CD genetics to clinical subphenotypes have not been very successful. We hypothesized that the large number of confirmed genetic variants enables (better) classification of CD patients. 
Methodology/Principal Findings: To look for genetic-based subgroups, genotyping results of 46 SNPs identified from CD GWAS were analyzed by Latent Class Analysis (LCA) in CD patients and in healthy controls. Six genetic-based subgroups were identified in CD patients, which were significantly different from the five subgroups found in healthy controls. The identified CD-specific clusters are therefore likely to contribute to disease behavior. We then looked at whether we could relate the genetic-based subgroups to the currently used clinical parameters. Although modest differences in prevalence of disease location and behavior could be observed among the CD clusters, Random Forest analysis showed that patients could not be allocated to one of the 6 genetic-based subgroups based on the typically used clinical parameters alone. This points to a poor relationship between the genetic-based subgroups and the used clinical subphenotypes. 
Conclusions/Significance: This approach serves as a first step to reclassify Crohn's disease. The used technique can be applied to other common},
  articleno    = {e12952},
  author       = {Cleynen, Isabemme and John, Jestinah M Mahachie and Henckaerts, Liesbet and Van Moerkercke, Wouter and Rutgeerts, Paul and Van Steen, Kristel and Vermeire, Severine},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keywords     = {INFLAMMATORY-BOWEL-DISEASE,GENOME-WIDE ASSOCIATION,SUSCEPTIBILITY LOCI,CLASSIFICATION,AUTOPHAGY,GENOTYPE,COHORT,RISK},
  language     = {eng},
  number       = {9},
  pages        = {7},
  title        = {Molecular reclassification of Crohn's disease by cluster analysis of genetic variants},
  url          = {http://dx.doi.org/10.1371/journal.pone.0012952},
  volume       = {5},
  year         = {2010},
}

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