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

<h4>Background</h4>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 3...

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Autores principales:	Isabelle Cleynen, Jestinah M Mahachie John, Liesbet Henckaerts, Wouter Van Moerkercke, Paul Rutgeerts, Kristel Van Steen, Severine Vermeire
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5584e0a296c64000804547fa77340fb2
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spelling	oai:doaj.org-article:5584e0a296c64000804547fa77340fb22021-11-18T06:34:53ZMolecular reclassification of Crohn's disease by cluster analysis of genetic variants.1932-620310.1371/journal.pone.0012952https://doaj.org/article/5584e0a296c64000804547fa77340fb22010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20886065/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>This approach serves as a first step to reclassify Crohn's disease. The used technique can be applied to other common complex diseases as well, and will help to complete patient characterization, in order to evolve towards personalized medicine.Isabelle CleynenJestinah M Mahachie JohnLiesbet HenckaertsWouter Van MoerkerckePaul RutgeertsKristel Van SteenSeverine VermeirePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 9, p e12952 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Isabelle Cleynen Jestinah M Mahachie John Liesbet Henckaerts Wouter Van Moerkercke Paul Rutgeerts Kristel Van Steen Severine Vermeire Molecular reclassification of Crohn's disease by cluster analysis of genetic variants.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>This approach serves as a first step to reclassify Crohn's disease. The used technique can be applied to other common complex diseases as well, and will help to complete patient characterization, in order to evolve towards personalized medicine.
format	article
author	Isabelle Cleynen Jestinah M Mahachie John Liesbet Henckaerts Wouter Van Moerkercke Paul Rutgeerts Kristel Van Steen Severine Vermeire
author_facet	Isabelle Cleynen Jestinah M Mahachie John Liesbet Henckaerts Wouter Van Moerkercke Paul Rutgeerts Kristel Van Steen Severine Vermeire
author_sort	Isabelle Cleynen
title	Molecular reclassification of Crohn's disease by cluster analysis of genetic variants.
title_short	Molecular reclassification of Crohn's disease by cluster analysis of genetic variants.
title_full	Molecular reclassification of Crohn's disease by cluster analysis of genetic variants.
title_fullStr	Molecular reclassification of Crohn's disease by cluster analysis of genetic variants.
title_full_unstemmed	Molecular reclassification of Crohn's disease by cluster analysis of genetic variants.
title_sort	molecular reclassification of crohn's disease by cluster analysis of genetic variants.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/5584e0a296c64000804547fa77340fb2
work_keys_str_mv	AT isabellecleynen molecularreclassificationofcrohnsdiseasebyclusteranalysisofgeneticvariants AT jestinahmmahachiejohn molecularreclassificationofcrohnsdiseasebyclusteranalysisofgeneticvariants AT liesbethenckaerts molecularreclassificationofcrohnsdiseasebyclusteranalysisofgeneticvariants AT woutervanmoerkercke molecularreclassificationofcrohnsdiseasebyclusteranalysisofgeneticvariants AT paulrutgeerts molecularreclassificationofcrohnsdiseasebyclusteranalysisofgeneticvariants AT kristelvansteen molecularreclassificationofcrohnsdiseasebyclusteranalysisofgeneticvariants AT severinevermeire molecularreclassificationofcrohnsdiseasebyclusteranalysisofgeneticvariants
_version_	1718424478617174016

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

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