Genome-wide association study of image-based emphysema scoring in the Swedish CArdioPulmonary bioImage Study (SCAPIS) suggests two new risk loci in smokers.

IF 5.7 2区医学 Q1 Medicine

Respiratory Research Pub Date : 2026-08-08 DOI:10.1186/s12931-026-03853-6

Fredrik Nyberg, Per Lundmark, Anders Blomberg, Koen Dekkers, Arne Egesten, Jonas Eriksson Ström, Bruna Gigante, Anders Gummesson, Cecilia Gunnarsson, Christer Janson, Andrei Malinovschi, Anna-Carin Olin, Marju Orho-Melander, Hans Lennart Persson, Ida Pesonen, Magnus Sköld, Stefan Söderberg, Hanan Tanash, Lowie E G W Vanfleteren, Tove Fall

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引用次数: 0

Abstract

Background: Despite the high prevalence and clinical significance of emphysema, few genetic risk loci have been consistently replicated. We conducted a genome-wide association study (GWAS) of CT-based emphysema, with a particular focus on non-smoking-related genetic determinants.

Methods: We analyzed 25,639 individuals of European ancestry from the SCAPIS national cohort, aged 50-65 years, of which 51% were never-smokers. Emphysema was assessed through semi-quantitative visual scoring of CT scans. GWAS was performed in the whole sample and stratified on smoking status. We also examined the association of previously reported emphysema- and lung function-related variants with emphysema in our dataset.

Results: Emphysema criteria were fulfilled for 1,479 participants (5.6%), with higher prevalence among current (N = 576, 18.2%) and former smokers (N = 612, 6.5%) compared to never-smokers (N = 263, 2.0%). We identified three independent genetic loci for emphysema in smokers and no signals in never-smokers. The strongest signal was observed in the well-established nicotinic acetylcholine receptor cluster (CHRNA5-A3-B4) locus on chromosome 15. Additionally, we discovered novel associations near the dysferlin (DYSF) gene on chromosome 2 and in an intergenic region on chromosome 3. By assessing previously lung phenotype-associated variants we also found evidence supporting association with emphysema in smokers for variants in the EFEMP1/MIR217HG/PNPT1 locus on chromosome 2, previously linked to reduced FEV₁/FVC ratio.

Conclusion: This study, based on the largest unselected population sample to date, provides novel insights into the genetic architecture of emphysema. However, no signals were detected in never-smokers despite the large sample-size, likely due to the low prevalence of emphysema in that group. The proposed genetic risk loci require external replication.

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瑞典心肺生物图像研究（SCAPIS）中基于图像的肺气肿评分的全基因组关联研究提示吸烟者中有两个新的危险位点。

背景：尽管肺气肿的发病率和临床意义很高，但很少有遗传风险位点被一致地复制。我们进行了一项基于ct的肺气肿全基因组关联研究（GWAS），特别关注非吸烟相关的遗传决定因素。方法：我们分析了来自SCAPIS国家队列的25,639名欧洲血统的个体，年龄在50-65岁之间，其中51%是从不吸烟的。通过CT扫描的半定量视觉评分来评估肺气肿。GWAS在整个样本中进行，并根据吸烟状况分层。在我们的数据集中，我们还检查了先前报道的肺气肿和肺功能相关变异与肺气肿的关系。结果：1479名参与者（5.6%）符合肺气肿标准，当前吸烟者（N = 576,18.2%）和曾经吸烟者（N = 612, 6.5%）的患病率高于从不吸烟者（N = 263, 2.0%）。我们在吸烟者中发现了三个独立的肺气肿基因位点，而在不吸烟者中没有信号。在第15号染色体上已建立的烟碱乙酰胆碱受体簇（CHRNA5-A3-B4）位点上观察到最强的信号。此外，我们还在2号染色体和3号染色体的基因间区发现了新的关联。通过评估先前的肺表型相关变异，我们还发现了支持吸烟者肺气肿与2号染色体上EFEMP1/MIR217HG/PNPT1位点变异相关的证据，该位点先前与FEV1/FVC比率降低有关。结论：该研究基于迄今为止最大的未选择人群样本，为肺气肿的遗传结构提供了新的见解。然而，尽管样本量很大，但在从不吸烟者中没有检测到信号，这可能是由于该组中肺气肿患病率较低。提出的遗传风险位点需要外部复制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Respiratory Research RESPIRATORY SYSTEM-

CiteScore

9.70

自引率

1.70%

发文量

314

审稿时长

4-8 weeks

期刊介绍： Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.