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Cluster analysis in severe emphysema subjects using phenotype and genotype data: an exploratory investigation.

Abstract：

BACKGROUND:Numerous studies have demonstrated associations between genetic markers and COPD, but results have been inconsistent. One reason may be heterogeneity in disease definition. Unsupervised learning approaches may assist in understanding disease heterogeneity. METHODS:We selected 31 phenotypic variables and 12 SNPs from five candidate genes in 308 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study cohort. We used factor analysis to select a subset of phenotypic variables, and then used cluster analysis to identify subtypes of severe emphysema. We examined the phenotypic and genotypic characteristics of each cluster. RESULTS:We identified six factors accounting for 75% of the shared variability among our initial phenotypic variables. We selected four phenotypic variables from these factors for cluster analysis: 1) post-bronchodilator FEV1 percent predicted, 2) percent bronchodilator responsiveness, and quantitative CT measurements of 3) apical emphysema and 4) airway wall thickness. K-means cluster analysis revealed four clusters, though separation between clusters was modest: 1) emphysema predominant, 2) bronchodilator responsive, with higher FEV1; 3) discordant, with a lower FEV1 despite less severe emphysema and lower airway wall thickness, and 4) airway predominant. Of the genotypes examined, membership in cluster 1 (emphysema-predominant) was associated with TGFB1 SNP rs1800470. CONCLUSIONS:Cluster analysis may identify meaningful disease subtypes and/or groups of related phenotypic variables even in a highly selected group of severe emphysema subjects, and may be useful for genetic association studies.

journal_name

Respir Res

journal_title

Respiratory research

authors

Cho MH,Washko GR,Hoffmann TJ,Criner GJ,Hoffman EA,Martinez FJ,Laird N,Reilly JJ,Silverman EK

doi

10.1186/1465-9921-11-30

subject

Has Abstract

pub_date

2010-03-16 00:00:00

pages

30

eissn

1465-9921

issn

1465-993X

pii

1465-9921-11-30

journal_volume

11

pub_type

杂志文章

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