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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/187852
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oai:ri.conicet.gov.ar:11336/187852 |
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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 Técnicas2025-09-29T10:26:07Zoai: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:34982025-09-29 10:26:07.989CONICET 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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1844614261342470144 |
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13.070432 |