Genetic Advances in Chronic Obstructive Pulmonary Disease Insights from COPDGene
Genetic Advances in Chronic Obstructive Pulmonary Disease Insights from COPDGene
复制标题
慢性阻塞性肺疾病的遗传学研究进展--从COPD基因的角度
DOI：
10.1164/rccm.201808-1455so
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发表时间：
2019-09-15
影响因子：
24.7
通讯作者：
Silverman, Edwin K.
中科院分区：
文献类型：
--
作者：
Ragland, Margaret F.;Benway, Christopher J.;Silverman, Edwin K.
慢性阻塞性肺疾病（COPD）是一种常见的进行性疾病，受遗传和环境因素的影响。多年来，对COPD遗传基础的了解仅限于孟德尔综合征，如α-1抗胰蛋白酶缺乏症和由罕见遗传变异引起的皮肤松弛拉克萨。在过去的十年中，全基因组关联研究的激增，全基因组测序的可及性，以及分析遗传变异数据的新方法的发展，导致对在COPD易感性和COPD相关表型中发挥作用的遗传变异的理解大幅增加。COPD基因（COPD遗传流行病学）是一项多中心、纵向研究，涉及10，000多名当前和以前的吸烟者，对于理解COPD遗传基础的这些突破至关重要。迄今为止，超过20个遗传基因座已令人信服地与COPD患病状态相关，另外的基因座证明与COPD相关表型如肺气肿、慢性支气管炎和低氧血症相关。在这篇综述中，我们讨论了COPD基因研究对发现这些遗传关联的贡献，以及正在进行的COPD亚型、蛋白质生物标志物和后全基因组关联研究分析的遗传学研究。
Chronic obstructive pulmonary disease (COPD) is a common and progressive disease that is influenced by both genetic and environmental factors. For many years, knowledge of the genetic basis of COPD was limited to Mendelian syndromes, such as alpha-1 antitrypsin deficiency and cutis laxa, caused by rare genetic variants. Over the past decade, the proliferation of genome-wide association studies, the accessibility of whole-genome sequencing, and the development of novel methods for analyzing genetic variation data have led to a substantial increase in the understanding of genetic variants that play a role in COPD susceptibility and COPD-related phenotypes. COPDGene (Genetic Epidemiology of COPD), a multicenter, longitudinal study of over 10,000 current and former cigarette smokers, has been pivotal to these breakthroughs in understanding the genetic basis of COPD. To date, over 20 genetic loci have been convincingly associated with COPD affection status, with additional loci demonstrating association with COPD-related phenotypes such as emphysema, chronic bronchitis, and hypoxemia. In this review, we discuss the contributions of the COPDGene study to the discovery of these genetic associations as well as the ongoing genetic investigations of COPD subtypes, protein biomarkers, and post-genome-wide association study analysis.