Journal article
Integrated Genomic Analyses in Bronchopulmonary Dysplasia
The Journal of pediatrics, Vol.166(3), pp.531-537.e13
03/2015
DOI: 10.1016/j.jpeds.2014.09.052
PMCID: PMC4344889
PMID: 25449221
Abstract
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.
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.
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.
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.
Details
- Title: Subtitle
- Integrated Genomic Analyses in Bronchopulmonary Dysplasia
- Creators
- Namasivayam Ambalavanan - Department of Pediatrics, University of Alabama at Birmingham, Birmingham, ALC. Michael Cotten - Department of Pediatrics, Duke University, Durham, NCGrier P Page - RTI International, Atlanta, GAWaldemar A Carlo - Department of Pediatrics, University of Alabama at Birmingham, Birmingham, ALJeffrey C Murray - Department of Pediatrics, University of Iowa, Iowa City, IASoumyaroop Bhattacharya - Division of Neonatology and Program in Pediatric Molecular and Personalized Medicine, University of Rochester, Rochester, NYThomas J Mariani - Division of Neonatology and Program in Pediatric Molecular and Personalized Medicine, University of Rochester, Rochester, NYAlain C Cuna - Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MOOna M Faye-Petersen - Department of Pathology, University of Alabama at Birmingham, Birmingham, ALDavid Kelly - Department of Pathology, University of Alabama at Birmingham, Birmingham, ALRosemary D Higgins - Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD
- Resource Type
- Journal article
- Publication Details
- The Journal of pediatrics, Vol.166(3), pp.531-537.e13
- DOI
- 10.1016/j.jpeds.2014.09.052
- PMID
- 25449221
- PMCID
- PMC4344889
- NLM abbreviation
- J Pediatr
- ISSN
- 0022-3476
- eISSN
- 1097-6833
- Publisher
- Elsevier Inc
- Grant note
- U01 HG4423 / National Human Genome Research Institute (http://dx.doi.org/10.13039/100000051) M01 RR30; M01 RR32; M01 RR39; M01 RR70; M01 RR80; M01 RR633; M01 RR750; M01 RR997; M01 RR6022; M01 RR7122; M01 RR8084; M01 RR16587; UL1 RR24979 / National Institutes of Health (http://dx.doi.org/10.13039/100000002) U01 HD36790; U10 HD21364; U10 HD21373; U10 HD21385; U10 HD21397; U10 HD21415; U10 HD27851; U10 HD27853; U10 HD27856; U10 HD27871; U10 HD27880; U10 HD27881; U10 HD27904; U10 HD34216; U10 HD40461; U10 HD40492; U10 HD40498; U10 HD40689; U10 HD53109 / Eunice Kennedy Shriver NICHD
- Language
- English
- Date published
- 03/2015
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025343102771
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