{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:12:08Z","timestamp":1787314328898,"version":"build-2736575974"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["CUTTIN18XX1"],"award-info":[{"award-number":["CUTTIN18XX1"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["BAMSHA18XX0"],"award-info":[{"award-number":["BAMSHA18XX0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["KNOWLE18XX0"],"award-info":[{"award-number":["KNOWLE18XX0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FRN 167282"],"award-info":[{"award-number":["FRN 167282"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000082","name":"Cystic Fibrosis Canada","doi-asserted-by":"publisher","award":["2626"],"award-info":[{"award-number":["2626"]}],"id":[{"id":"10.13039\/501100000082","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008762","name":"Genome Canada","doi-asserted-by":"publisher","award":["OGI-148"],"award-info":[{"award-number":["OGI-148"]}],"id":[{"id":"10.13039\/100008762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013873","name":"Government of Ontario","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013873","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["CUTTIN18XX1"],"award-info":[{"award-number":["CUTTIN18XX1"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["BAMSHA18XX0"],"award-info":[{"award-number":["BAMSHA18XX0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["KNOWLE18XX0"],"award-info":[{"award-number":["KNOWLE18XX0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["FRN 167282"],"award-info":[{"award-number":["FRN 167282"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Canada","doi-asserted-by":"publisher","award":["2626"],"award-info":[{"award-number":["2626"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Genome Canada","doi-asserted-by":"publisher","award":["OGI-148"],"award-info":[{"award-number":["OGI-148"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Government of Ontario","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Lung disease is the major cause of morbidity and mortality in persons with cystic fibrosis (pwCF). Variability in CF lung disease has substantial non-CFTR (CF transmembrane conductance regulator) genetic influence. Identification of genetic modifiers has prognostic and therapeutic importance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Identify genetic modifier loci and genes\/pathways associated with pulmonary disease severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Whole-genome sequencing data on 4,248 unique pwCF with pancreatic insufficiency and lung function measures were combined with imputed genotypes from an additional 3,592 patients with pancreatic insufficiency from the United States, Canada, and France. This report describes association of approximately 15.9 million SNPs using the quantitative Kulich normal residual mortality-adjusted (KNoRMA) lung disease phenotype in 7,840 pwCF using premodulator lung function data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Testing included common and rare SNPs, transcriptome-wide association, gene-level, and pathway analyses. Pathway analyses identified novel associations with genes that have key roles in organ development, and we hypothesize that these genes may relate to dysanapsis and\/or variability in lung repair. Results confirmed and extended previous genome-wide association study findings. These whole-genome sequencing data provide finely mapped genetic information to support mechanistic studies. No novel primary associations with common single variants or rare variants were found. Multilocus effects at chr5p13 (SLC9A3\/CEP72) and chr11p13 (EHF\/APIP) were identified. Variant effect size estimates at associated loci were consistently ordered across the cohorts, indicating possible age or birth cohort effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This premodulator genomic, transcriptomic, and pathway association study of 7,840 pwCF will facilitate mechanistic and postmodulator genetic studies and the development of novel therapeutics for CF lung disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202209-1653oc","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T14:25:50Z","timestamp":1678890350000},"page":"1324-1333","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":39,"title":["Genetic Modifiers of Cystic Fibrosis Lung Disease Severity: Whole-Genome Analysis of 7,840 Patients"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4092-7463","authenticated-orcid":false,"given":"Yi-Hui","family":"Zhou","sequence":"first","affiliation":[{"name":"Bioinformatics Research Center"},{"name":"Department of Biological Sciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Gallins","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda G.","family":"Pace","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute\/UNC CF Research Center, School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Dang","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute\/UNC CF Research Center, School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melis A.","family":"Aksit","sequence":"additional","affiliation":[{"name":"McKusick-Nathans Department of Genetic Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth E.","family":"Blue","sequence":"additional","affiliation":[{"name":"Brotman Baty Institute for Precision Medicine, Seattle, Washington"},{"name":"Division of Medical Genetics, Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kati J.","family":"Buckingham","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph M.","family":"Collaco","sequence":"additional","affiliation":[{"name":"Eudowood Division of Pediatric Respiratory Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna V.","family":"Faino","sequence":"additional","affiliation":[{"name":"Children\u2019s Core for Biostatistics, Epidemiology and Analytics in Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt N.","family":"Hetrick","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Center for Inherited Disease Research, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Center for Inherited Disease Research, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frankline M.","family":"Onchiri","sequence":"additional","affiliation":[{"name":"Children\u2019s Core for Biostatistics, Epidemiology and Analytics in Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kymberleigh","family":"Pagel","sequence":"additional","affiliation":[{"name":"The Institute for Computational Medicine, The Johns Hopkins University, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth W.","family":"Pugh","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Center for Inherited Disease Research, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen S.","family":"Raraigh","sequence":"additional","affiliation":[{"name":"McKusick-Nathans Department of Genetic Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Rosenfeld","sequence":"additional","affiliation":[{"name":"Center for Clinical and Translational Research, Seattle Children\u2019s Research Institute, Seattle, Washington"},{"name":"Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biostatistics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Genetics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics"},{"name":"Department of Genetics, and"},{"name":"Department of Computer Science, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harriet","family":"Corvol","sequence":"additional","affiliation":[{"name":"Pediatric Pulmonary Department, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Trousseau, Paris, France"},{"name":"Centre de Recherche Saint Antoine, Sorbonne Universit\u00e9, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa J.","family":"Strug","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Dalla Lana School of Public Health"},{"name":"Program in Genetics and Genome Biology and"},{"name":"Department of Statistical Sciences, and"},{"name":"The Center for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada"},{"name":"Department of Computer Science, University of Toronto, Toronto, Ontario, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Bamshad","sequence":"additional","affiliation":[{"name":"Brotman Baty Institute for Precision Medicine, Seattle, Washington"},{"name":"Division of Genetic Medicine, Department of Pediatrics"},{"name":"Department of Genome Sciences, University of Washington, Seattle, Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4532-6421","authenticated-orcid":false,"given":"Scott M.","family":"Blackman","sequence":"additional","affiliation":[{"name":"McKusick-Nathans Department of Genetic Medicine"},{"name":"Division of Pediatric Endocrinology, Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garry R.","family":"Cutting","sequence":"additional","affiliation":[{"name":"McKusick-Nathans Department of Genetic Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald L.","family":"Gibson","sequence":"additional","affiliation":[{"name":"Center for Clinical and Translational Research, Seattle Children\u2019s Research Institute, Seattle, Washington"},{"name":"Department of Pediatrics, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanda K.","family":"O\u2019Neal","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute\/UNC CF Research Center, School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred A.","family":"Wright","sequence":"additional","affiliation":[{"name":"Bioinformatics Research Center"},{"name":"Department of Biological Sciences, and"},{"name":"Department of Statistics, North Carolina State University, Raleigh, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Knowles","sequence":"additional","affiliation":[{"name":"Marsico Lung Institute\/UNC CF Research Center, School of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,15]]},"reference":[{"key":"2026012204440370100_bib1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/nrg3849","article-title":"Cystic fibrosis genetics: from molecular understanding to clinical application","volume":"16","author":"Cutting","year":"2015","journal-title":"Nat Rev Genet"},{"key":"2026012204440370100_bib2","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.jcf.2019.11.001","article-title":"Genetic variation in CFTR and modifier loci may modulate cystic fibrosis disease severity","volume":"19","author":"Paranjapye","year":"2020","journal-title":"J Cyst Fibros"},{"key":"2026012204440370100_bib3","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1164\/rccm.200608-1164OC","article-title":"Heritability of lung disease severity in cystic fibrosis","volume":"175","author":"Vanscoy","year":"2007","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204440370100_bib4","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1146\/annurev-genom-083117-021329","article-title":"Cystic fibrosis disease modifiers: complex genetics defines the phenotypic diversity in a monogenic disease","volume":"19","author":"O\u2019Neal","year":"2018","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"2026012204440370100_bib5","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1097\/MOP.0000000000000892","article-title":"Cystic fibrosis transmembrane conductance receptor modulator therapy in cystic fibrosis, an update","volume":"32","author":"Egan","year":"2020","journal-title":"Curr Opin Pediatr"},{"key":"2026012204440370100_bib6","doi-asserted-by":"crossref","first-page":"8382","DOI":"10.1038\/ncomms9382","article-title":"Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis","volume":"6","author":"Corvol","year":"2015","journal-title":"Nat Commun"},{"key":"2026012204440370100_bib7","doi-asserted-by":"crossref","first-page":"e0239189","DOI":"10.1371\/journal.pone.0239189","article-title":"Mining GWAS and eQTL data for CF lung disease modifiers by gene expression imputation","volume":"15","author":"Dang","year":"2020","journal-title":"PLoS One"},{"key":"2026012204440370100_bib8","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.jcf.2021.10.011","article-title":"Complete CFTR gene sequencing in 5,058 individuals with cystic fibrosis informs variant-specific treatment","volume":"21","author":"Raraigh","year":"2022","journal-title":"J Cyst Fibros"},{"key":"2026012204440370100_bib9","doi-asserted-by":"crossref","first-page":"S306","DOI":"10.1016\/S1569-1993(21)02067-1","article-title":"Genetic variants that modify severity of CF lung disease: update from the CF genome project","volume":"20","author":"Zhou","year":"2021","journal-title":"J Cyst Fibros"},{"key":"2026012204440370100_bib10","first-page":"100090","article-title":"Leveraging TOPMed imputation server and constructing a cohort-specific imputation reference panel to enhance genotype imputation among cystic fibrosis patients","volume":"3","author":"Sun","year":"2022","journal-title":"HGG Adv"},{"key":"2026012204440370100_bib11","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1513\/AnnalsATS.201511-781OC","article-title":"The Cystic Fibrosis Foundation Patient Registry. Design and methods of a national observational disease registry","volume":"13","author":"Knapp","year":"2016","journal-title":"Ann Am Thorac Soc"},{"key":"2026012204440370100_bib12","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/gepi.20297","article-title":"Estimation of significance thresholds for genomewide association scans","volume":"32","author":"Dudbridge","year":"2008","journal-title":"Genet Epidemiol"},{"key":"2026012204440370100_bib13","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1534\/genetics.114.167908","article-title":"Identifying causal variants at loci with multiple signals of association","volume":"198","author":"Hormozdiari","year":"2014","journal-title":"Genetics"},{"key":"2026012204440370100_bib14","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","article-title":"The Ensembl variant effect predictor","volume":"17","author":"McLaren","year":"2016","journal-title":"Genome Biol"},{"key":"2026012204440370100_bib15","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/ng.3506","article-title":"Integrative approaches for large-scale transcriptome-wide association studies","volume":"48","author":"Gusev","year":"2016","journal-title":"Nat Genet"},{"key":"2026012204440370100_bib16","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1126\/science.aaz1776","article-title":"The GTEx Consortium atlas of genetic regulatory effects across human tissues","volume":"369","author":"GTEx Consortium","year":"2020","journal-title":"Science"},{"key":"2026012204440370100_bib17","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1017\/thg.2019.93","article-title":"The Netherlands Twin Register: longitudinal research based on twin and twin-family designs","volume":"22","author":"Ligthart","year":"2019","journal-title":"Twin Res Hum Genet"},{"key":"2026012204440370100_bib18","doi-asserted-by":"crossref","first-page":"7111","DOI":"10.1038\/s41598-021-86536-0","article-title":"Modular genome-wide gene expression architecture shared by early traits of osteoporosis and atherosclerosis in the Young Finns Study","volume":"11","author":"Mishra","year":"2021","journal-title":"Sci Rep"},{"key":"2026012204440370100_bib19","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1017\/thg.2014.79","article-title":"VEGAS2: software for more flexible gene-based testing","volume":"18","author":"Mishra","year":"2015","journal-title":"Twin Res Hum Genet"},{"key":"2026012204440370100_bib20","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026012204440370100_bib21","first-page":"100141","article-title":"clusterProfiler 4.0: a universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation (Camb)"},{"key":"2026012204440370100_bib22","first-page":"100117","article-title":"Accounting for population structure in genetic studies of cystic fibrosis","volume":"3","author":"Kingston","year":"2022","journal-title":"HGG Adv"},{"key":"2026012204440370100_bib23","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.ajhg.2014.12.022","article-title":"Gene expression in transformed lymphocytes reveals variation in endomembrane and HLA pathways modifying cystic fibrosis pulmonary phenotypes","volume":"96","author":"O\u2019Neal","year":"2015","journal-title":"Am J Hum Genet"},{"key":"2026012204440370100_bib24","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1164\/rccm.201701-0134OC","article-title":"Airway mucosal host defense is key to genomic regulation of cystic fibrosis lung disease severity","volume":"197","author":"Polineni","year":"2018","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204440370100_bib25","doi-asserted-by":"crossref","first-page":"5265","DOI":"10.3390\/ijms23095265","article-title":"Hedgehog signaling pathway orchestrates human lung branching morphogenesis","volume":"23","author":"Belgacemi","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2026012204440370100_bib26","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.3390\/ijms19082460","article-title":"TGF-\u03b2 signaling in lung health and disease","volume":"19","author":"Saito","year":"2018","journal-title":"Int J Mol Sci"},{"key":"2026012204440370100_bib27","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/s42003-021-02118-w","article-title":"Wnt signaling in lung development, regeneration, and disease progression","volume":"4","author":"Aros","year":"2021","journal-title":"Commun Biol"},{"key":"2026012204440370100_bib28","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1152\/physrev.00001.2018","article-title":"Building and regenerating the lung cell by cell","volume":"99","author":"Whitsett","year":"2019","journal-title":"Physiol Rev"},{"key":"2026012204440370100_bib29","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1152\/jappl.1974.37.1.67","article-title":"Variability of maximum expiratory flow-volume curves","volume":"37","author":"Green","year":"1974","journal-title":"J Appl Physiol"},{"key":"2026012204440370100_bib30","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1001\/jama.2020.6918","article-title":"Association of dysanapsis with chronic obstructive pulmonary disease among older adults","volume":"323","author":"Smith","year":"2020","journal-title":"JAMA"},{"key":"2026012204440370100_bib31","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1164\/rccm.202007-3025LE","article-title":"Central airway tree dysanapsis extends to the peripheral airways","volume":"203","author":"Vameghestahbanati","year":"2021","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204440370100_bib32","doi-asserted-by":"crossref","first-page":"E974","DOI":"10.1073\/pnas.1715564115","article-title":"Human airway branch variation and chronic obstructive pulmonary disease","volume":"115","author":"Smith","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026012204440370100_bib33","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1136\/thoraxjnl-2017-211216","article-title":"The effect of early growth patterns and lung function on the development of childhood asthma: a population based study","volume":"73","author":"Casas","year":"2018","journal-title":"Thorax"},{"key":"2026012204440370100_bib34","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1152\/japplphysiol.00263.2017","article-title":"Postnatal airway growth in cystic fibrosis piglets","volume":"123","author":"Adam","year":"2017","journal-title":"J Appl Physiol (1985)"},{"key":"2026012204440370100_bib35","doi-asserted-by":"crossref","first-page":"21975","DOI":"10.1038\/srep21975","article-title":"The extracellular calcium-sensing receptor regulates human fetal lung development via CFTR","volume":"6","author":"Brennan","year":"2016","journal-title":"Sci Rep"},{"key":"2026012204440370100_bib36","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1002\/ppul.22922","article-title":"Tracheomalacia is associated with lower FEV1 and Pseudomonas acquisition in children with CF","volume":"49","author":"Fischer","year":"2014","journal-title":"Pediatr Pulmonol"},{"key":"2026012204440370100_bib37","doi-asserted-by":"crossref","first-page":"1900382","DOI":"10.1183\/13993003.00382-2019","article-title":"ERS statement on tracheomalacia and bronchomalacia in children","volume":"54","author":"Wallis","year":"2019","journal-title":"Eur Respir J"},{"key":"2026012204440370100_bib38","doi-asserted-by":"crossref","first-page":"L1145","DOI":"10.1152\/ajplung.00006.2020","article-title":"Resveratrol restores intracellular transport in cystic fibrosis epithelial cells","volume":"318","author":"Lu","year":"2020","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026012204440370100_bib39","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1080\/10409238.2018.1442408","article-title":"Protein kinase C: perfectly balanced","volume":"53","author":"Newton","year":"2018","journal-title":"Crit Rev Biochem Mol Biol"},{"key":"2026012204440370100_bib40","doi-asserted-by":"crossref","first-page":"F165","DOI":"10.1152\/ajprenal.00628.2011","article-title":"Calcineurin homologous protein: a multifunctional Ca2+-binding protein family","volume":"303","author":"Di Sole","year":"2012","journal-title":"Am J Physiol Renal Physiol"},{"key":"2026012204440370100_bib41","doi-asserted-by":"crossref","first-page":"1902269","DOI":"10.1183\/13993003.02269-2019","article-title":"Genome-wide association study in patients with pulmonary Mycobacterium avium complex disease","volume":"58","author":"Namkoong","year":"2021","journal-title":"Eur Respir J"},{"key":"2026012204440370100_bib42","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1164\/rccm.201810-1972OC","article-title":"XBP1S regulates MUC5B in a promoter variant-dependent pathway in IPF airway epithelia","volume":"200","author":"Chen","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012204440370100_bib43","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.ajhg.2021.12.012","article-title":"A flexible summary statistics-based colocalization method with application to the mucin cystic fibrosis lung disease modifier locus","volume":"109","author":"Wang","year":"2022","journal-title":"Am J Hum Genet"},{"key":"2026012204440370100_bib44","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.gene.2017.07.068","article-title":"Association of clinical severity of cystic fibrosis with variants in the SLC gene family (SLC6A14, SLC26A9, SLC11A1 and SLC9A3)","volume":"629","author":"Pereira","year":"2017","journal-title":"Gene"},{"key":"2026012204440370100_bib45","doi-asserted-by":"crossref","DOI":"10.1101\/2022.03.28.22272580","article-title":"A cystic fibrosis lung disease modifier locus harbors tandem repeats associated with gene expression","author":"Roshandel","year":"2022"},{"key":"2026012204440370100_bib46","doi-asserted-by":"crossref","first-page":"L317","DOI":"10.1152\/ajplung.00126.2016","article-title":"Ibuprofen regulation of microtubule dynamics in cystic fibrosis epithelial cells","volume":"311","author":"Rymut","year":"2016","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026012204440370100_bib47","doi-asserted-by":"crossref","first-page":"L1081","DOI":"10.1152\/ajplung.00369.2018","article-title":"Acetyl-CoA carboxylase inhibition regulates microtubule dynamics and intracellular transport in cystic fibrosis epithelial cells","volume":"316","author":"Rymut","year":"2019","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026012204440370100_bib48","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ajhg.2018.11.008","article-title":"Leveraging polygenic functional enrichment to improve GWAS power","volume":"104","author":"Kichaev","year":"2019","journal-title":"Am J Hum Genet"},{"key":"2026012204440370100_bib49","doi-asserted-by":"crossref","first-page":"e48476","DOI":"10.7554\/eLife.48476","article-title":"Systematic genetic analysis of the MHC region reveals mechanistic underpinnings of HLA type associations with disease","volume":"8","author":"D\u2019Antonio","year":"2019","journal-title":"eLife"},{"key":"2026012204440370100_bib50","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1016\/j.humimm.2019.05.018","article-title":"HLA alleles and haplotypes observed in 263 US families","volume":"80","author":"Osoegawa","year":"2019","journal-title":"Hum Immunol"},{"key":"2026012204440370100_bib51","doi-asserted-by":"crossref","first-page":"16020","DOI":"10.1038\/hgv.2016.20","article-title":"Novel variation at chr11p13 associated with cystic fibrosis lung disease severity","volume":"3","author":"Dang","year":"2016","journal-title":"Hum Genome Var"},{"key":"2026012204440370100_bib52","doi-asserted-by":"crossref","first-page":"7726","DOI":"10.1111\/jcmm.14646","article-title":"Coordinate regulation of ELF5 and EHF at the chr11p13 CF modifier region","volume":"23","author":"Swahn","year":"2019","journal-title":"J Cell Mol Med"},{"key":"2026012204440370100_bib53","doi-asserted-by":"crossref","first-page":"8773","DOI":"10.1093\/nar\/gkx482","article-title":"Regulatory dynamics of 11p13 suggest a role for EHF in modifying CF lung disease severity","volume":"45","author":"Stolzenburg","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"2026012204440370100_bib54","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jcf.2018.05.013","article-title":"AGTR2 absence or antagonism prevents cystic fibrosis pulmonary manifestations","volume":"18","author":"Darrah","year":"2019","journal-title":"J Cyst Fibros"},{"key":"2026012204440370100_bib55","doi-asserted-by":"crossref","first-page":"e1008007","DOI":"10.1371\/journal.pgen.1008007","article-title":"Genetic association and transcriptome integration identify contributing genes and tissues at cystic fibrosis modifier loci","volume":"15","author":"Gong","year":"2019","journal-title":"PLoS Genet"},{"key":"2026012204440370100_bib56","doi-asserted-by":"crossref","first-page":"3311","DOI":"10.1007\/s00018-020-03487-x","article-title":"Update on SLC6A14 in lung and gastrointestinal physiology and physiopathology: focus on cystic fibrosis","volume":"77","author":"Ruffin","year":"2020","journal-title":"Cell Mol Life Sci"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/207\/10\/1324\/66436163\/ajrccm_207_10_1324.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/207\/10\/1324\/66436163\/ajrccm_207_10_1324.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T09:44:18Z","timestamp":1769075058000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/207\/10\/1324\/8428041"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5]]},"references-count":56,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,5,15]]},"published-print":{"date-parts":[[2023,5,15]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.202209-1653oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,5]]},"published":{"date-parts":[[2023,5]]},"assertion":[{"value":"2022-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}