{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T08:48:33Z","timestamp":1758271713231,"version":"3.44.0"},"reference-count":33,"publisher":"European Respiratory Society (ERS)","issue":"3","license":[{"start":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T00:00:00Z","timestamp":1749081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publications.ersnet.org\/user-licence"}],"funder":[{"name":"Jiangsu Provincial Medical Innovation Center of Orthopedic Surgery","award":["CXZX202214"],"award-info":[{"award-number":["CXZX202214"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971346, 81670003"],"award-info":[{"award-number":["81971346, 81670003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2025,5,13]]},"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Primary spontaneous pneumothorax is a rare disease commonly found in young adults, with unknown aetiology. We aimed to investigate the susceptibility genes and the downstream signalling involved in the development of primary spontaneous pneumothorax.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted the first large-scale genome-wide association study (GWAS) composed of 2223 patients and 3838 controls. The functional role of the novel susceptibility loci was investigated by both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> assays. Gene expression profiling in lung epithelial cell lines was performed, and conditional gene knockout mice were generated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified four novel susceptibility loci at 14q32.2 near <jats:italic>C14orf177<\/jats:italic>, at 15q26.3 near <jats:italic>CHSY1<\/jats:italic>, at 16q23.1 near <jats:italic>CFDP1<\/jats:italic> and at 22q13.1 near <jats:italic>CBX7<\/jats:italic>. The fine-mapping of 22q13.1 revealed a functional variant which regulated <jats:italic>CBX7<\/jats:italic> expression by disrupting the binding activity of transcription factor CREB1. Conditional knockout of <jats:italic>Cbx7<\/jats:italic> in mouse lung epithelial cells resulted in lung cyst formation. Meanwhile, downregulation of the <jats:italic>CBX7<\/jats:italic> elevated the expression of <jats:italic>MMP9<\/jats:italic> and <jats:italic>MMP16<\/jats:italic>, which are part of extracellular matrix regulators and may lead to lung injury.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our GWAS discovered four novel susceptibility loci of primary spontaneous pneumothorax and presented a mechanistic basis for the genetic association with primary spontaneous pneumothorax. The novel susceptibility gene <jats:italic>CBX7<\/jats:italic> and downstream <jats:italic>MMP<\/jats:italic> signalling give a new clue to the pathogenesis of primary spontaneous pneumothorax.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1183\/13993003.02110-2024","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T10:45:19Z","timestamp":1749120319000},"page":"2402110","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Genome-wide association study reveals <i>CBX7<\/i> as a novel susceptibility gene associated with primary spontaneous pneumothorax in the Chinese Han 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