Department of Health Sciences, University of Leicester, Leicester, UK.
Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Nat Genet. 2019 Mar;51(3):481-493. doi: 10.1038/s41588-018-0321-7. Epub 2019 Feb 25.
Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
肺功能下降预示着死亡率的增加，也是慢性阻塞性肺疾病（COPD）的关键诊断依据。在一项针对 400102 名欧洲血统个体的全基因组关联研究中，我们定义了 279 个肺功能信号，其中 139 个是新的。这些变体结合在一起，可在独立人群中强烈预测 COPD。此外，这些变体的综合效应在吸烟者和不吸烟者以及不同祖先群体中具有可推广性。我们强调了 COPD 的生物学途径、已知和潜在的药物靶点，以及在表型全基因组关联研究中，与肺功能相关的变体的自身免疫相关和其他多效性效应。这种新的遗传证据有可能改善未来 COPD 的预防和治疗策略。
