1 Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York.
2 Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Am J Respir Crit Care Med. 2018 Jul 15;198(2):208-219. doi: 10.1164/rccm.201707-1493OC.
Lung function and chronic obstructive pulmonary disease (COPD) are heritable traits. Genome-wide association studies (GWAS) have identified numerous pulmonary function and COPD loci, primarily in cohorts of European ancestry.
Perform a GWAS of COPD phenotypes in Hispanic/Latino populations to identify loci not previously detected in European populations.
GWAS of lung function and COPD in Hispanic/Latino participants from a population-based cohort. We performed replication studies of novel loci in independent studies.
Among 11,822 Hispanic/Latino participants, we identified eight novel signals; three replicated in independent populations of European Ancestry. A novel locus for FEV in ZSWIM7 (rs4791658; P = 4.99 × 10) replicated. A rare variant (minor allele frequency = 0.002) in HAL (rs145174011) was associated with FEV/FVC (P = 9.59 × 10) in a region previously identified for COPD-related phenotypes; it remained significant in conditional analyses but did not replicate. Admixture mapping identified a novel region, with a variant in AGMO (rs41331850), associated with Amerindian ancestry and FEV, which replicated. A novel locus for FEV identified among ever smokers (rs291231; P = 1.92 × 10) approached statistical significance for replication in admixed populations of African ancestry, and a novel SNP for COPD in PDZD2 (rs7709630; P = 1.56 × 10) regionally replicated. In addition, loci previously identified for lung function in European samples were associated in Hispanic/Latino participants in the Hispanic Community Health Study/Study of Latinos at the genome-wide significance level.
We identified novel signals for lung function and COPD in a Hispanic/Latino cohort. Including admixed populations when performing genetic studies may identify variants contributing to genetic etiologies of COPD.
肺功能和慢性阻塞性肺疾病（COPD）是可遗传的特征。全基因组关联研究（GWAS）已经确定了许多肺功能和 COPD 基因座，主要是在欧洲血统的队列中。
在西班牙裔/拉丁裔人群中进行 COPD 表型的 GWAS，以鉴定以前在欧洲人群中未发现的基因座。
对基于人群的队列中的西班牙裔/拉丁裔参与者进行肺功能和 COPD 的 GWAS。我们对新发现的基因座在独立研究中进行了复制研究。
在 11822 名西班牙裔/拉丁裔参与者中，我们确定了 8 个新信号；其中 3 个在欧洲血统的独立人群中得到复制。一个新的 ZSWIM7 基因座上的 FEV 变异（rs4791658；P=4.99×10）得到了复制。HAL 基因座上的一个罕见变异（次要等位基因频率=0.002）（rs145174011）与 FEV/FVC 相关（P=9.59×10），该基因座在先前确定的 COPD 相关表型区域中具有显著意义；在条件分析中仍然显著，但没有得到复制。混合映射确定了一个新的区域，AGMO 基因座上的一个变异（rs41331850）与美洲印第安人血统和 FEV 相关，该变异得到了复制。在曾经吸烟的人群中发现的一个新的 FEV 基因座（rs291231；P=1.92×10）在具有非洲血统的混合人群中进行复制时接近统计学意义，而 PDZD2 基因座上的一个 COPD 新 SNP（rs7709630；P=1.56×10）在区域内得到了复制。此外，在欧洲样本中先前确定的与肺功能相关的基因座在西班牙裔/拉丁裔参与者的西班牙裔社区健康研究/拉丁裔研究中达到了全基因组显著水平。
我们在西班牙裔/拉丁裔队列中确定了新的肺功能和 COPD 信号。在进行遗传研究时纳入混合人群可能会鉴定出导致 COPD 遗传病因的变异。
