PT  - JOURNAL ARTICLE
AU  - Peter J Castaldi
AU  - Jennifer Dy
AU  - James Ross
AU  - Yale Chang
AU  - George R Washko
AU  - Douglas Curran-Everett
AU  - Andre Williams
AU  - David A Lynch
AU  - Barry J Make
AU  - James D Crapo
AU  - Russ P Bowler
AU  - Elizabeth A Regan
AU  - John E Hokanson
AU  - Greg L Kinney
AU  - Meilan K Han
AU  - Xavier Soler
AU  - Joseph W Ramsdell
AU  - R Graham Barr
AU  - Marilyn Foreman
AU  - Edwin van Beek
AU  - Richard Casaburi
AU  - Gerald J Criner
AU  - Sharon M Lutz
AU  - Steven I Rennard
AU  - Stephanie Santorico
AU  - Frank C Sciurba
AU  - Dawn L DeMeo
AU  - Craig P Hersh
AU  - Edwin K Silverman
AU  - Michael H Cho
TI  - Cluster analysis in the COPDGene study identifies subtypes of smokers with distinct patterns of airway disease and emphysema
AID  - 10.1136/thoraxjnl-2013-203601
DP  - 2014 May 01
TA  - Thorax
PG  - 416--423
VI  - 69
IP  - 5
4099  - http://thorax.bmj.com/content/69/5/416.short
4100  - http://thorax.bmj.com/content/69/5/416.full
SO  - Thorax2014 May 01; 69
AB  - Background There is notable heterogeneity in the clinical presentation of patients with COPD. To characterise this heterogeneity, we sought to identify subgroups of smokers by applying cluster analysis to data from the COPDGene study. Methods We applied a clustering method, k-means, to data from 10 192 smokers in the COPDGene study. After splitting the sample into a training and validation set, we evaluated three sets of input features across a range of k (user-specified number of clusters). Stable solutions were tested for association with four COPD-related measures and five genetic variants previously associated with COPD at genome-wide significance. The results were confirmed in the validation set. Findings We identified four clusters that can be characterised as (1) relatively resistant smokers (ie, no/mild obstruction and minimal emphysema despite heavy smoking), (2) mild upper zone emphysema-predominant, (3) airway disease-predominant and (4) severe emphysema. All clusters are strongly associated with COPD-related clinical characteristics, including exacerbations and dyspnoea (p<0.001). We found strong genetic associations between the mild upper zone emphysema group and rs1980057 near HHIP, and between the severe emphysema group and rs8034191 in the chromosome 15q region (p<0.001). All significant associations were replicated at p<0.05 in the validation sample (12/12 associations with clinical measures and 2/2 genetic associations). Interpretation Cluster analysis identifies four subgroups of smokers that show robust associations with clinical characteristics of COPD and known COPD-associated genetic variants.