Molecular reclassification of Crohn's disease: a cautionary note on population stratification.
Complex human diseases commonly differ in their phenotypic characteristics, e.g., Crohn's disease (CD) patients are heterogeneous with regard to disease location and disease extent. The genetic susceptibility to Crohn's disease is widely acknowledged and has been demonstrated by identifica...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3798408?pdf=render |
| _version_ | 1819154830248116224 |
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| author | Bärbel Maus Camille Jung Jestinah M Mahachie John Jean-Pierre Hugot Emmanuelle Génin Kristel Van Steen |
| author_facet | Bärbel Maus Camille Jung Jestinah M Mahachie John Jean-Pierre Hugot Emmanuelle Génin Kristel Van Steen |
| author_sort | Bärbel Maus |
| collection | DOAJ |
| description | Complex human diseases commonly differ in their phenotypic characteristics, e.g., Crohn's disease (CD) patients are heterogeneous with regard to disease location and disease extent. The genetic susceptibility to Crohn's disease is widely acknowledged and has been demonstrated by identification of over 100 CD associated genetic loci. However, relating CD subphenotypes to disease susceptible loci has proven to be a difficult task. In this paper we discuss the use of cluster analysis on genetic markers to identify genetic-based subgroups while taking into account possible confounding by population stratification. We show that it is highly relevant to consider the confounding nature of population stratification in order to avoid that detected clusters are strongly related to population groups instead of disease-specific groups. Therefore, we explain the use of principal components to correct for population stratification while clustering affected individuals into genetic-based subgroups. The principal components are obtained using 30 ancestry informative markers (AIM), and the first two PCs are determined to discriminate between continental origins of the affected individuals. Genotypes on 51 CD associated single nucleotide polymorphisms (SNPs) are used to perform latent class analysis, hierarchical and Partitioning Around Medoids (PAM) cluster analysis within a sample of affected individuals with and without the use of principal components to adjust for population stratification. It is seen that without correction for population stratification clusters seem to be influenced by population stratification while with correction clusters are unrelated to continental origin of individuals. |
| first_indexed | 2024-12-22T15:27:19Z |
| format | Article |
| id | doaj.art-f1fef2f499dd4bca9925a2f7bb3fbe43 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T15:27:19Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f1fef2f499dd4bca9925a2f7bb3fbe432022-12-21T18:21:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7772010.1371/journal.pone.0077720Molecular reclassification of Crohn's disease: a cautionary note on population stratification.Bärbel MausCamille JungJestinah M Mahachie JohnJean-Pierre HugotEmmanuelle GéninKristel Van SteenComplex human diseases commonly differ in their phenotypic characteristics, e.g., Crohn's disease (CD) patients are heterogeneous with regard to disease location and disease extent. The genetic susceptibility to Crohn's disease is widely acknowledged and has been demonstrated by identification of over 100 CD associated genetic loci. However, relating CD subphenotypes to disease susceptible loci has proven to be a difficult task. In this paper we discuss the use of cluster analysis on genetic markers to identify genetic-based subgroups while taking into account possible confounding by population stratification. We show that it is highly relevant to consider the confounding nature of population stratification in order to avoid that detected clusters are strongly related to population groups instead of disease-specific groups. Therefore, we explain the use of principal components to correct for population stratification while clustering affected individuals into genetic-based subgroups. The principal components are obtained using 30 ancestry informative markers (AIM), and the first two PCs are determined to discriminate between continental origins of the affected individuals. Genotypes on 51 CD associated single nucleotide polymorphisms (SNPs) are used to perform latent class analysis, hierarchical and Partitioning Around Medoids (PAM) cluster analysis within a sample of affected individuals with and without the use of principal components to adjust for population stratification. It is seen that without correction for population stratification clusters seem to be influenced by population stratification while with correction clusters are unrelated to continental origin of individuals.http://europepmc.org/articles/PMC3798408?pdf=render |
| spellingShingle | Bärbel Maus Camille Jung Jestinah M Mahachie John Jean-Pierre Hugot Emmanuelle Génin Kristel Van Steen Molecular reclassification of Crohn's disease: a cautionary note on population stratification. PLoS ONE |
| title | Molecular reclassification of Crohn's disease: a cautionary note on population stratification. |
| title_full | Molecular reclassification of Crohn's disease: a cautionary note on population stratification. |
| title_fullStr | Molecular reclassification of Crohn's disease: a cautionary note on population stratification. |
| title_full_unstemmed | Molecular reclassification of Crohn's disease: a cautionary note on population stratification. |
| title_short | Molecular reclassification of Crohn's disease: a cautionary note on population stratification. |
| title_sort | molecular reclassification of crohn s disease a cautionary note on population stratification |
| url | http://europepmc.org/articles/PMC3798408?pdf=render |
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