{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T04:00:09Z","timestamp":1770350409291,"version":"3.49.0"},"reference-count":0,"publisher":"European Respiratory Society (ERS)","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016239","name":"Ministerie van Economische Zaken, Landbouw en Innovatie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016239","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Provinces in the North of the Netherlands"},{"DOI":"10.13039\/501100005075","name":"Universitair Medisch Centrum Groningen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005075","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002999","name":"Ministerie van Volksgezondheid, Welzijn en Sport","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002999","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UI\/BD\/151337\/2021"],"award-info":[{"award-number":["UI\/BD\/151337\/2021"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004344","name":"Stichting Astma Bestrijding","doi-asserted-by":"publisher","award":["SAB 2013-013"],"award-info":[{"award-number":["SAB 2013-013"]}],"id":[{"id":"10.13039\/501100004344","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["ERJ Open Res"],"accepted":{"date-parts":[[2026,1,15]]},"abstract":"\n Rationale<\/jats:title>\n Variations in age-related lung function decline are associated with genetic and environmental factors. The genetic variants contributing to this decline remain largely unknown, limiting the understanding of individual susceptibility and potential interventions.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n This study aims to uncover the genetic factors associated with lung function decline, using the Lifelines cohort study.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Longitudinal data covering 3 visits over approximately 15\u2005years were available. Genotyping and longitudinal spirometry data were present for 24\u2009749 subjects aged 25 or older at baseline. A three-step approach was used. First, lung function change over time was estimated using a linear-mixed effect model. Second, a genome-wide association study for the estimated change was conducted, adjusting for age, sex, smoking load and the first 10 principal components. Third, single nucleotide polymorphisms (SNPs) with p-value <1\u00d710\n \u22125<\/jats:sup>\n were analysed using a linear-mixed effect model. Selected SNPs were tested in two independent cohorts (N=1376 and N=27\u2009249), followed by meta-analysis.\n <\/jats:p>\n <\/jats:sec>\n \n Measurements and Main Results<\/jats:title>\n \n Among the included individuals, 19\u2009722 had spirometry at two timepoints and 5027 at three, with median [IQR] follow-up of 8.1 [4.4, 10.4] and 12.1 [11, 13.6] years, respectively. We identified 67 variants suggestively associated with lung function decline (p<1\u00d710\n \u22125<\/jats:sup>\n ). Rs150094594, was significant (p=0.007) in a replication cohort with consistent effect direction. This intergenic variant, not previously reported, reached genome-wide significance in the meta-analysis (rs150094594:T, \u03b2(\n se<\/jats:sc>\n ): 15.9(2.7)\u2005ml\/year, p-value=3.9\u00d710\n \u22129<\/jats:sup>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This study shows a role of genetics in lung function decline, emphasizing the importance of exploring the interplay between genetic and environmental factors.<\/jats:p>\n <\/jats:sec>","DOI":"10.1183\/23120541.00987-2025","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T14:15:32Z","timestamp":1770300932000},"page":"00987-2025","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic variants underpinning lung function decline in the Lifelines general population cohort study"],"prefix":"10.1183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0699-335X","authenticated-orcid":false,"given":"Rui","family":"Mar\u00e7alo","sequence":"first","affiliation":[]},{"given":"Corry-Anke","family":"Brandsma","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8450-3518","authenticated-orcid":false,"given":"Peter J.","family":"van der Most","sequence":"additional","affiliation":[]},{"given":"Alda","family":"Marques","sequence":"additional","affiliation":[]},{"given":"Gabriela R.","family":"Moura","sequence":"additional","affiliation":[]},{"given":"Maarten","family":"van den Berge","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7531-4547","authenticated-orcid":false,"given":"Judith M.","family":"Vonk","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7210-8174","authenticated-orcid":false,"given":"Maaike","family":"de Vries","sequence":"additional","affiliation":[]}],"member":"81","published-online":{"date-parts":[[2026,2,5]]},"container-title":["ERJ Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/23120541.00987-2025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T14:15:32Z","timestamp":1770300932000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/23120541.00987-2025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,5]]},"references-count":0,"alternative-id":["10.1183\/23120541.00987-2025"],"URL":"https:\/\/doi.org\/10.1183\/23120541.00987-2025","relation":{},"ISSN":["2312-0541"],"issn-type":[{"value":"2312-0541","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,5]]}}}