Genome-wide association study of image-based emphysema scoring in the Swedish CArdioPulmonary bioImage Study (SCAPIS) suggests two new risk loci in smokers.
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Nyberg F, Lundmark P, Blomberg A, Dekkers K, Egesten A, Eriksson Ström J, Gigante B, Gummesson A, Gunnarsson C, Janson C, Malinovschi A, Olin AC, Orho-Melander M, Persson HL, Pesonen I, Sköld M, Söderberg S, Tanash H, Vanfleteren LEGW, Fall T
Respir. Res. 27 (1) - [2026-08-08; online 2026-08-08]
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. 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. 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. 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.
NGI Uppsala (SNP&SEQ Technology Platform) [Service]
National Genomics Infrastructure [Service]
PubMed 42634071
DOI 10.1186/s12931-026-03853-6
Crossref 10.1186/s12931-026-03853-6
pmc: PMC13501701
pii: 10.1186/s12931-026-03853-6