Epigenome-wide association study of bronchopulmonary dysplasia in preterm infants: results from the discovery-BPD program

Autores
Wang, Xuting; Cho, Hye Youn; Campbell, Michelle R.; Panduri, Vijayalakshmi; Coviello, Silvina Andrea; Caballero, Mauricio Tomás; Sambandan, Deepa; Kleeberger, Steven R.; Polack, Fernando Pedro; Ofman, Gaston; Bell, Douglas A.
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Bronchopulmonary dysplasia (BPD) is a lung disease in premature infants caused by therapeutic oxygen supplemental and characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD have been increasing with limited therapeutic options for prevention and treatment. This study was designed to explore the relationship between gestational age (GA), birth weight, and estimated blood cell-type composition in premature infants and to elucidate early epigenetic biomarkers associated with BPD.Methods: Cord blood DNA from preterm neonates that went on to develop BPD (n = 14) or not (non-BPD, n = 93) was applied to Illumina 450 K methylation arrays. Blood cell-type compositions were estimated using DNA methylation profiles. Multivariable robust regression analysis elucidated CpGs associated with BPD risk. cDNA microarray analysis of cord blood RNA identified differentially expressed genes in neonates who later developed BPD.Results: The development of BPD and the need for oxygen supplementation were strongly associated with GA (BPD, p < 1.0E−04; O2 supplementation, p < 1.0E−09) and birth weight (BPD, p < 1.0E−02; O2 supplementation, p < 1.0E−07). The estimated nucleated red blood cell (NRBC) percent was negatively associated with birth weight and GA, positively associated with hypomethylation of the tobacco smoke exposure biomarker cg05575921, and high-NRBC blood samplesdisplayed a hypomethylation profile. Epigenome-wide association study (EWAS) identified 38 (Bonferroni) and 275 (false discovery rate 1%) differentially methylated CpGs associated with BPD. BPD-associated CpGs in cord blood were enriched for lung maturation and hematopoiesis pathways. Stochastic epigenetic mutation burden at birth was significantly elevated among those who developed BPD (adjusted p = 0.02). Transcriptome changes in cord blood cells reflected cell cycle, development, and pulmonary disorder events in BPD.Conclusions: While results must be interpreted with caution because of the small size of this study, NRBC content strongly impacted DNA methylation profiles in preterm cord blood and EWAS analysis revealed potential insights into biological pathways involved in BPD pathogenesis.
Fil: Wang, Xuting. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Cho, Hye Youn. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Campbell, Michelle R.. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Panduri, Vijayalakshmi. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Coviello, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina
Fil: Caballero, Mauricio Tomás. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sambandan, Deepa. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Kleeberger, Steven R.. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados Unidos
Fil: Ofman, Gaston. Fundación para la Investigación en Infectología Infantil; Argentina
Fil: Bell, Douglas A.. National Institute of Environmental Health Sciences; Estados Unidos
Materia
Displasia broncopulmonar
prematurez
epigenetica
Epigenome-wide association
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/187852
Acceder
id CONICETDig_bede7d676dbf3ca53314b216be939257
oai_identifier_str oai:ri.conicet.gov.ar:11336/187852
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Epigenome-wide association study of bronchopulmonary dysplasia in preterm infants: results from the discovery-BPD programWang, XutingCho, Hye YounCampbell, Michelle R.Panduri, VijayalakshmiCoviello, Silvina AndreaCaballero, Mauricio TomásSambandan, DeepaKleeberger, Steven R.Polack, Fernando PedroOfman, GastonBell, Douglas A.Displasia broncopulmonarprematurezepigeneticaEpigenome-wide associationhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Bronchopulmonary dysplasia (BPD) is a lung disease in premature infants caused by therapeutic oxygen supplemental and characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD have been increasing with limited therapeutic options for prevention and treatment. This study was designed to explore the relationship between gestational age (GA), birth weight, and estimated blood cell-type composition in premature infants and to elucidate early epigenetic biomarkers associated with BPD.Methods: Cord blood DNA from preterm neonates that went on to develop BPD (n = 14) or not (non-BPD, n = 93) was applied to Illumina 450 K methylation arrays. Blood cell-type compositions were estimated using DNA methylation profiles. Multivariable robust regression analysis elucidated CpGs associated with BPD risk. cDNA microarray analysis of cord blood RNA identified differentially expressed genes in neonates who later developed BPD.Results: The development of BPD and the need for oxygen supplementation were strongly associated with GA (BPD, p < 1.0E−04; O2 supplementation, p < 1.0E−09) and birth weight (BPD, p < 1.0E−02; O2 supplementation, p < 1.0E−07). The estimated nucleated red blood cell (NRBC) percent was negatively associated with birth weight and GA, positively associated with hypomethylation of the tobacco smoke exposure biomarker cg05575921, and high-NRBC blood samplesdisplayed a hypomethylation profile. Epigenome-wide association study (EWAS) identified 38 (Bonferroni) and 275 (false discovery rate 1%) differentially methylated CpGs associated with BPD. BPD-associated CpGs in cord blood were enriched for lung maturation and hematopoiesis pathways. Stochastic epigenetic mutation burden at birth was significantly elevated among those who developed BPD (adjusted p = 0.02). Transcriptome changes in cord blood cells reflected cell cycle, development, and pulmonary disorder events in BPD.Conclusions: While results must be interpreted with caution because of the small size of this study, NRBC content strongly impacted DNA methylation profiles in preterm cord blood and EWAS analysis revealed potential insights into biological pathways involved in BPD pathogenesis.Fil: Wang, Xuting. National Institute of Environmental Health Sciences; Estados UnidosFil: Cho, Hye Youn. National Institute of Environmental Health Sciences; Estados UnidosFil: Campbell, Michelle R.. National Institute of Environmental Health Sciences; Estados UnidosFil: Panduri, Vijayalakshmi. National Institute of Environmental Health Sciences; Estados UnidosFil: Coviello, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Caballero, Mauricio Tomás. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Sambandan, Deepa. National Institute of Environmental Health Sciences; Estados UnidosFil: Kleeberger, Steven R.. National Institute of Environmental Health Sciences; Estados UnidosFil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados UnidosFil: Ofman, Gaston. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Bell, Douglas A.. National Institute of Environmental Health Sciences; Estados UnidosBioMed Central2022-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/187852Wang, Xuting; Cho, Hye Youn; Campbell, Michelle R.; Panduri, Vijayalakshmi; Coviello, Silvina Andrea; et al.; Epigenome-wide association study of bronchopulmonary dysplasia in preterm infants: results from the discovery-BPD program; BioMed Central; Clinical Epigenetics; 14; 1; 4-2022; 1-201868-70751868-7083CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-022-01272-0info:eu-repo/semantics/altIdentifier/doi/10.1186/s13148-022-01272-0info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:58:48Zoai:ri.conicet.gov.ar:11336/187852instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:58:48.453CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Epigenome-wide association study of bronchopulmonary dysplasia in preterm infants: results from the discovery-BPD program
title Epigenome-wide association study of bronchopulmonary dysplasia in preterm infants: results from the discovery-BPD program
spellingShingle Epigenome-wide association study of bronchopulmonary dysplasia in preterm infants: results from the discovery-BPD program
Wang, Xuting
Displasia broncopulmonar
prematurez
epigenetica
Epigenome-wide association
title_short Epigenome-wide association study of bronchopulmonary dysplasia in preterm infants: results from the discovery-BPD program
title_full Epigenome-wide association study of bronchopulmonary dysplasia in preterm infants: results from the discovery-BPD program
title_fullStr Epigenome-wide association study of bronchopulmonary dysplasia in preterm infants: results from the discovery-BPD program
title_full_unstemmed Epigenome-wide association study of bronchopulmonary dysplasia in preterm infants: results from the discovery-BPD program
title_sort Epigenome-wide association study of bronchopulmonary dysplasia in preterm infants: results from the discovery-BPD program
dc.creator.none.fl_str_mv Wang, Xuting
Cho, Hye Youn
Campbell, Michelle R.
Panduri, Vijayalakshmi
Coviello, Silvina Andrea
Caballero, Mauricio Tomás
Sambandan, Deepa
Kleeberger, Steven R.
Polack, Fernando Pedro
Ofman, Gaston
Bell, Douglas A.
author Wang, Xuting
author_facet Wang, Xuting
Cho, Hye Youn
Campbell, Michelle R.
Panduri, Vijayalakshmi
Coviello, Silvina Andrea
Caballero, Mauricio Tomás
Sambandan, Deepa
Kleeberger, Steven R.
Polack, Fernando Pedro
Ofman, Gaston
Bell, Douglas A.
author_role author
author2 Cho, Hye Youn
Campbell, Michelle R.
Panduri, Vijayalakshmi
Coviello, Silvina Andrea
Caballero, Mauricio Tomás
Sambandan, Deepa
Kleeberger, Steven R.
Polack, Fernando Pedro
Ofman, Gaston
Bell, Douglas A.
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Displasia broncopulmonar
prematurez
epigenetica
Epigenome-wide association
topic Displasia broncopulmonar
prematurez
epigenetica
Epigenome-wide association
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Bronchopulmonary dysplasia (BPD) is a lung disease in premature infants caused by therapeutic oxygen supplemental and characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD have been increasing with limited therapeutic options for prevention and treatment. This study was designed to explore the relationship between gestational age (GA), birth weight, and estimated blood cell-type composition in premature infants and to elucidate early epigenetic biomarkers associated with BPD.Methods: Cord blood DNA from preterm neonates that went on to develop BPD (n = 14) or not (non-BPD, n = 93) was applied to Illumina 450 K methylation arrays. Blood cell-type compositions were estimated using DNA methylation profiles. Multivariable robust regression analysis elucidated CpGs associated with BPD risk. cDNA microarray analysis of cord blood RNA identified differentially expressed genes in neonates who later developed BPD.Results: The development of BPD and the need for oxygen supplementation were strongly associated with GA (BPD, p < 1.0E−04; O2 supplementation, p < 1.0E−09) and birth weight (BPD, p < 1.0E−02; O2 supplementation, p < 1.0E−07). The estimated nucleated red blood cell (NRBC) percent was negatively associated with birth weight and GA, positively associated with hypomethylation of the tobacco smoke exposure biomarker cg05575921, and high-NRBC blood samplesdisplayed a hypomethylation profile. Epigenome-wide association study (EWAS) identified 38 (Bonferroni) and 275 (false discovery rate 1%) differentially methylated CpGs associated with BPD. BPD-associated CpGs in cord blood were enriched for lung maturation and hematopoiesis pathways. Stochastic epigenetic mutation burden at birth was significantly elevated among those who developed BPD (adjusted p = 0.02). Transcriptome changes in cord blood cells reflected cell cycle, development, and pulmonary disorder events in BPD.Conclusions: While results must be interpreted with caution because of the small size of this study, NRBC content strongly impacted DNA methylation profiles in preterm cord blood and EWAS analysis revealed potential insights into biological pathways involved in BPD pathogenesis.
Fil: Wang, Xuting. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Cho, Hye Youn. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Campbell, Michelle R.. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Panduri, Vijayalakshmi. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Coviello, Silvina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Investigación en Infectología Infantil; Argentina
Fil: Caballero, Mauricio Tomás. Fundación para la Investigación en Infectología Infantil; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Sambandan, Deepa. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Kleeberger, Steven R.. National Institute of Environmental Health Sciences; Estados Unidos
Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; Argentina. Vanderbilt University; Estados Unidos
Fil: Ofman, Gaston. Fundación para la Investigación en Infectología Infantil; Argentina
Fil: Bell, Douglas A.. National Institute of Environmental Health Sciences; Estados Unidos
description Background: Bronchopulmonary dysplasia (BPD) is a lung disease in premature infants caused by therapeutic oxygen supplemental and characterized by impaired pulmonary development which persists into later life. While advances in neonatal care have improved survival rates of premature infants, cases of BPD have been increasing with limited therapeutic options for prevention and treatment. This study was designed to explore the relationship between gestational age (GA), birth weight, and estimated blood cell-type composition in premature infants and to elucidate early epigenetic biomarkers associated with BPD.Methods: Cord blood DNA from preterm neonates that went on to develop BPD (n = 14) or not (non-BPD, n = 93) was applied to Illumina 450 K methylation arrays. Blood cell-type compositions were estimated using DNA methylation profiles. Multivariable robust regression analysis elucidated CpGs associated with BPD risk. cDNA microarray analysis of cord blood RNA identified differentially expressed genes in neonates who later developed BPD.Results: The development of BPD and the need for oxygen supplementation were strongly associated with GA (BPD, p < 1.0E−04; O2 supplementation, p < 1.0E−09) and birth weight (BPD, p < 1.0E−02; O2 supplementation, p < 1.0E−07). The estimated nucleated red blood cell (NRBC) percent was negatively associated with birth weight and GA, positively associated with hypomethylation of the tobacco smoke exposure biomarker cg05575921, and high-NRBC blood samplesdisplayed a hypomethylation profile. Epigenome-wide association study (EWAS) identified 38 (Bonferroni) and 275 (false discovery rate 1%) differentially methylated CpGs associated with BPD. BPD-associated CpGs in cord blood were enriched for lung maturation and hematopoiesis pathways. Stochastic epigenetic mutation burden at birth was significantly elevated among those who developed BPD (adjusted p = 0.02). Transcriptome changes in cord blood cells reflected cell cycle, development, and pulmonary disorder events in BPD.Conclusions: While results must be interpreted with caution because of the small size of this study, NRBC content strongly impacted DNA methylation profiles in preterm cord blood and EWAS analysis revealed potential insights into biological pathways involved in BPD pathogenesis.
publishDate 2022
dc.date.none.fl_str_mv 2022-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/187852
Wang, Xuting; Cho, Hye Youn; Campbell, Michelle R.; Panduri, Vijayalakshmi; Coviello, Silvina Andrea; et al.; Epigenome-wide association study of bronchopulmonary dysplasia in preterm infants: results from the discovery-BPD program; BioMed Central; Clinical Epigenetics; 14; 1; 4-2022; 1-20
1868-7075
1868-7083
CONICET Digital
CONICET
url http://hdl.handle.net/11336/187852
identifier_str_mv Wang, Xuting; Cho, Hye Youn; Campbell, Michelle R.; Panduri, Vijayalakshmi; Coviello, Silvina Andrea; et al.; Epigenome-wide association study of bronchopulmonary dysplasia in preterm infants: results from the discovery-BPD program; BioMed Central; Clinical Epigenetics; 14; 1; 4-2022; 1-20
1868-7075
1868-7083
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-022-01272-0
info:eu-repo/semantics/altIdentifier/doi/10.1186/s13148-022-01272-0
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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