Cluster analysis in the COPDGene study identifies subtypes of smokers with distinct patterns of airway disease and emphysema.
Cluster analysis in the COPDGene study identifies subtypes of smokers with distinct patterns of airway disease and emphysema.
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DOI：
10.1136/thoraxjnl-2013-203601
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发表时间：
2014-05
期刊：
影响因子：
10
通讯作者：
Cho MH
中科院分区：
文献类型：
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作者：
Castaldi PJ;Dy J;Ross J;Chang Y;Washko GR;Curran-Everett D;Williams A;Lynch DA;Make BJ;Crapo JD;Bowler RP;Regan EA;Hokanson JE;Kinney GL;Han MK;Soler X;Ramsdell JW;Barr RG;Foreman M;van Beek E;Casaburi R;Criner GJ;Lutz SM;Rennard SI;Santorico S;Sciurba FC;DeMeo DL;Hersh CP;Silverman EK;Cho MH
COPD患者的临床表现具有明显的异质性。为了表征这种异质性，我们试图通过对COPDgene研究的数据进行聚类分析来识别吸烟者的亚群。在COPDgene研究中，我们对10,192名吸烟者的数据应用了k-Means聚类方法。在将样本分成训练和验证集之后，我们评估了k(用户指定的聚类数)范围内的三组输入特征。稳定的解决方案被测试与四种与COPD相关的措施和五种以前在基因组范围内与COPD相关的遗传变异的相关性。结果在验证集中得到了确认。我们确定了四组特征：1)相对抵抗力强的吸烟者(即无/轻度梗阻和尽管大量吸烟但仍有轻微肺气肿)，2)轻度上区肺气肿占优势，3)呼吸道疾病占优势，4)重度肺气肿。所有聚集性疾病都与慢性阻塞性肺病相关的临床特征密切相关，包括病情恶化和呼吸困难(p<；0.001)。我们发现轻度上区肺气肿组与HIP附近的rs1980057和重度肺气肿组与染色体15q区域的rs8034191之间存在很强的遗传关联(p<；0.001)。所有有意义的关联在验证样本的p<；0.05处重复(12/12与临床测量相关，2/2与遗传相关)。聚类分析确定了四个吸烟者亚组，它们与COPD的临床特征和已知的COPD相关基因变异显示出强烈的相关性。
There is notable heterogeneity in the clinical presentation of patients with COPD. To characterize this heterogeneity, we sought to identify subgroups of smokers by applying cluster analysis to data from the COPDGene Study. 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. We identified four clusters that can be characterized as 1) relatively resistant smokers (i.e. 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 dyspnea (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). Cluster analysis identifies four subgroups of smokers that show robust associations with clinical characteristics of COPD and known COPD-associated genetic variants.
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影响因子：
5.8
作者：
Agusti A;Calverley PM;Celli B;Coxson HO;Edwards LD;Lomas DA;MacNee W;Miller BE;Rennard S;Silverman EK;Tal-Singer R;Wouters E;Yates JC;Vestbo J;Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) investigators
通讯作者：
Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) investigators
影响因子：
3.5
作者：
Cho, Michael H.;Castaldi, Peter J.;Silverman, Edwin K.
通讯作者：
Silverman, Edwin K.
DOI：
10.1198/016214508000000544
发表时间：
2008-09-01
影响因子：
3.7
作者：
Fraiman, Ricardo;Justel, Ana;Svarc, Marcela
通讯作者：
Svarc, Marcela
影响因子：
4.5
作者：
Pillai SG;Ge D;Zhu G;Kong X;Shianna KV;Need AC;Feng S;Hersh CP;Bakke P;Gulsvik A;Ruppert A;Lødrup Carlsen KC;Roses A;Anderson W;Rennard SI;Lomas DA;Silverman EK;Goldstein DB;ICGN Investigators
通讯作者：
ICGN Investigators
影响因子：
30.8
作者：
通讯作者：
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