Molecular reclassification of Crohn's disease: a cautionary note on population stratification.

[en] 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.

Disciplines :

Gastroenterology & hepatology

Author, co-author :

Maus, Barbel

Jung, Camille

Mahachie John, Jestinah ; Université de Liège - ULiège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Bioinformatique

Hugot, Jean-Pierre

Genin, Emmanuelle

Van Steen, Kristel ; Université de Liège - ULiège > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Bioinformatique

Language :

English

Title :

Molecular reclassification of Crohn's disease: a cautionary note on population stratification.

Publication date :

2013

Journal title :

PLoS ONE

eISSN :

1932-6203

Publisher :

Public Library of Science, United States - California

Volume :

Issue :

Pages :

e77720

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 19 April 2014

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