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Integrated genomic analyses in bronchopulmonary dysplasia.

Publication ,  Journal Article
Ambalavanan, N; Cotten, CM; Page, GP; Carlo, WA; Murray, JC; Bhattacharya, S; Mariani, TJ; Cuna, AC; Faye-Petersen, OM; Kelly, D; Higgins, RD ...
Published in: J Pediatr
March 2015

OBJECTIVE: To identify single-nucleotide polymorphisms (SNPs) and pathways associated with bronchopulmonary dysplasia (BPD) because O2 requirement at 36 weeks' postmenstrual age risk is strongly influenced by heritable factors. STUDY DESIGN: A genome-wide scan was conducted on 1.2 million genotyped SNPs, and an additional 7 million imputed SNPs, using a DNA repository of extremely low birth weight infants. Genome-wide association and gene set analysis was performed for BPD or death, severe BPD or death, and severe BPD in survivors. Specific targets were validated via the use of gene expression in BPD lung tissue and in mouse models. RESULTS: Of 751 infants analyzed, 428 developed BPD or died. No SNPs achieved genome-wide significance (P < 10(-8)), although multiple SNPs in adenosine deaminase, CD44, and other genes were just below P < 10(-6). Of approximately 8000 pathways, 75 were significant at false discovery rate (FDR) <0.1 and P < .001 for BPD/death, 95 for severe BPD/death, and 90 for severe BPD in survivors. The pathway with lowest FDR was miR-219 targets (P = 1.41E-08, FDR 9.5E-05) for BPD/death and phosphorous oxygen lyase activity (includes adenylate and guanylate cyclases) for both severe BPD/death (P = 5.68E-08, FDR 0.00019) and severe BPD in survivors (P = 3.91E-08, FDR 0.00013). Gene expression analysis confirmed significantly increased miR-219 and CD44 in BPD. CONCLUSIONS: Pathway analyses confirmed involvement of known pathways of lung development and repair (CD44, phosphorus oxygen lyase activity) and indicated novel molecules and pathways (adenosine deaminase, targets of miR-219) involved in genetic predisposition to BPD.

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Published In

J Pediatr

DOI

EISSN

1097-6833

Publication Date

March 2015

Volume

166

Issue

3

Start / End Page

531 / 7.e13

Location

United States

Related Subject Headings

  • United States
  • Survival Rate
  • Polymorphism, Single Nucleotide
  • Pediatrics
  • Mice
  • Infant, Premature
  • Infant, Newborn
  • Infant, Extremely Low Birth Weight
  • Infant
  • Incidence
 

Citation

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Chicago
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MLA
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Ambalavanan, N., Cotten, C. M., Page, G. P., Carlo, W. A., Murray, J. C., Bhattacharya, S., … Genomics and Cytokine Subcommittees of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, . (2015). Integrated genomic analyses in bronchopulmonary dysplasia. J Pediatr, 166(3), 531-7.e13. https://doi.org/10.1016/j.jpeds.2014.09.052
Ambalavanan, Namasivayam, C Michael Cotten, Grier P. Page, Waldemar A. Carlo, Jeffrey C. Murray, Soumyaroop Bhattacharya, Thomas J. Mariani, et al. “Integrated genomic analyses in bronchopulmonary dysplasia.J Pediatr 166, no. 3 (March 2015): 531-7.e13. https://doi.org/10.1016/j.jpeds.2014.09.052.
Ambalavanan N, Cotten CM, Page GP, Carlo WA, Murray JC, Bhattacharya S, et al. Integrated genomic analyses in bronchopulmonary dysplasia. J Pediatr. 2015 Mar;166(3):531-7.e13.
Ambalavanan, Namasivayam, et al. “Integrated genomic analyses in bronchopulmonary dysplasia.J Pediatr, vol. 166, no. 3, Mar. 2015, pp. 531-7.e13. Pubmed, doi:10.1016/j.jpeds.2014.09.052.
Ambalavanan N, Cotten CM, Page GP, Carlo WA, Murray JC, Bhattacharya S, Mariani TJ, Cuna AC, Faye-Petersen OM, Kelly D, Higgins RD, Genomics and Cytokine Subcommittees of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Integrated genomic analyses in bronchopulmonary dysplasia. J Pediatr. 2015 Mar;166(3):531–7.e13.
Journal cover image

Published In

J Pediatr

DOI

EISSN

1097-6833

Publication Date

March 2015

Volume

166

Issue

3

Start / End Page

531 / 7.e13

Location

United States

Related Subject Headings

  • United States
  • Survival Rate
  • Polymorphism, Single Nucleotide
  • Pediatrics
  • Mice
  • Infant, Premature
  • Infant, Newborn
  • Infant, Extremely Low Birth Weight
  • Infant
  • Incidence