Native American Ancestry, Lung Function, and COPD in Costa Ricans
Native American Ancestry, Lung Function, and COPD in Costa Ricans
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DOI：
10.1378/chest.13-1308
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发表时间：
2014-04-01
期刊：
影响因子：
9.6
通讯作者：
Celedon, Juan C.
中科院分区：
文献类型：
--
作者：
Chen, Wei;Brehm, John M.;Celedon, Juan C.
背景：在种族混合的西班牙裔人群中，美国原住民血统（NAA）是否与COPD或肺功能相关尚不清楚。方法：我们招募了578名患有和不患有COPD的哥斯达黎加人，纳入病例对照/基于家庭的混合队列，包括316名指标病例受试者的家庭成员。所有参与者都完成了问卷调查和肺活量测定，并提供了血样用于DNA提取。使用Illumina Human610-Quad和HumanOmniExpress BeadChip试剂盒（Illumina Inc .）进行全基因组基因分型，并根据这些基因型数据和参考面板估计个体祖先比例。对于无血缘关系的个体，采用线性或逻辑回归分析NAA与COPD （GOLD [Global Initiative For Chronic Obstructive Lung Disease] II期或以上）或肺功能的关系。对于大家庭，采用线性混合模型和广义估计方程进行分析。所有模型都根据年龄、性别、教育水平和吸烟行为进行了调整；FEV1模型也根据高度进行了调整。结果：参与者中欧洲、美洲原住民和非洲血统的平均比例分别为62%、35%和3%。在调整当前吸烟和其他协变量后，NAA与COPD呈负相关（OR每增加10%，0.55;95% CI, 0.41-0.75），但与FEV1、FVC和FEV1/FVC呈正相关。在对吸烟包年进行额外调整后，NAA与COPD或肺功能测量之间的关联略有减弱。我们发现，约31%的NAA对COPD的影响是由吸烟包年介导的。结论：哥斯达黎加人NAA与COPD呈负相关，但与FEV1或FVC呈正相关。祖先对吸烟行为的影响部分解释了COPD的发现，但不能解释FEV1或FVC。
Background: Whether Native American ancestry (NAA) is associated with COPD or lung function in a racially admixed Hispanic population is unknown.Methods: We recruited 578 Costa Ricans with and without COPD into a hybrid case-control/familybased cohort, including 316 members of families of index case subjects. All participants completed questionnaires and spirometry and gave a blood sample for DNA extraction. Genome-wide genotyping was conducted with the Illumina Human610-Quad and HumanOmniExpress BeadChip kits (Illumina Inc), and individual ancestral proportions were estimated from these genotypic data and reference panels. For unrelated individuals, linear or logistic regression was used for the analysis of NAA and COPD (GOLD [ Global Initiative for Chronic Obstructive Lung Disease] stage II or greater) or lung function. For extended families, linear mixed models and generalized estimating equations were used for the analysis. All models were adjusted for age, sex, educational level, and smoking behavior; models for FEV1 were also adjusted for height.Results: The average proportion of European, Native American, and African ancestry among participants was 62%, 35%, and 3%, respectively. After adjustment for current smoking and other covariates, NAA was inversely associated with COPD (OR per 10% increment, 0.55; 95% CI, 0.41-0.75) but positively associated with FEV1, FVC, and FEV1/FVC. After additional adjustment for pack-years of smoking, the association between NAA and COPD or lung function measures was slightly attenuated. We found that about 31% of the estimated effect of NAA on COPD is mediated by pack-years of smoking.Conclusions: NAA is inversely associated with COPD but positively associated with FEV1 or FVC in Costa Ricans. Ancestral effects on smoking behavior partly explain the findings for COPD but not for FEV1 or FVC.