A Genome-Wide Association Study (GWAS) for Bronchopulmonary Dysplasia
| Autor: | Jeffrey B. Gould, Laura L. Jelliffe-Pawlowski, John Oehlert, Krystal R. St. Julien, Hugh O'Brodovich, Laura C. Lazzeroni, Thomas J. Hoffmann, Cecele C. Quaintance, John S. Witte, Hui Wang, David K. Stevenson, Gary M. Shaw, Mark A. Krasnow |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Pathology Genome-wide association study Low Birth Weight and Health of the Newborn Medical and Health Sciences Pediatrics California Models Risk Factors Infant Mortality 2.1 Biological and endogenous factors Infant Very Low Birth Weight Medicine Exome Aetiology Lung Bronchopulmonary Dysplasia Pediatric education.field_of_study Single Nucleotide Phenotype Population study Female medicine.symptom medicine.medical_specialty Genotype Birth weight Population Gestational Age Single-nucleotide polymorphism chronic lung disease Polymorphism Single Nucleotide Article premature Neonatal Respiratory Distress Genetic Clinical Research Preterm Internal medicine very low birth weight infant Genetics Humans Genetic Predisposition to Disease Polymorphism education genome-wide association study Models Genetic business.industry Very Low Birth Weight Prevention Human Genome Psychology and Cognitive Sciences Infant Newborn Postmenstrual Age Genetic Variation Infant Perinatal Period - Conditions Originating in Perinatal Period Newborn medicine.disease Low birth weight Bronchopulmonary dysplasia Pediatrics Perinatology and Child Health business Genome-Wide Association Study |
| Zdroj: | Pediatrics, vol 132, iss 2 |
| ISSN: | 1098-4275 0031-4005 |
| DOI: | 10.1542/peds.2013-0533 |
| Popis: | OBJECTIVE: Twin studies suggest that heritability of moderate-severe bronchopulmonary dysplasia (BPD) is 53% to 79%, we conducted a genome-wide association study (GWAS) to identify genetic variants associated with the risk for BPD. METHODS: The discovery GWAS was completed on 1726 very low birth weight infants (gestational age = 25–296/7 weeks) who had a minimum of 3 days of intermittent positive pressure ventilation and were in the hospital at 36 weeks’ postmenstrual age. At 36 weeks’ postmenstrual age, moderate-severe BPD cases ( n = 899) were defined as requiring continuous supplemental oxygen, whereas controls ( n = 827) inhaled room air. An additional 795 comparable infants (371 cases, 424 controls) were a replication population. Genomic DNA from case and control newborn screening bloodspots was used for the GWAS. The replication study interrogated single-nucleotide polymorphisms (SNPs) identified in the discovery GWAS and those within the HumanExome beadchip. RESULTS: Genotyping using genomic DNA was successful. We did not identify SNPs associated with BPD at the genome-wide significance level (5 × 10−8) and no SNP identified in previous studies reached statistical significance (Bonferroni-corrected P value threshold .0018). Pathway analyses were not informative. CONCLUSIONS: We did not identify genomic loci or pathways that account for the previously described heritability for BPD. Potential explanations include causal mutations that are genetic variants and were not assayed or are mapped to many distributed loci, inadequate sample size, race ethnicity of our study population, or case-control differences investigated are not attributable to underlying common genetic variation. * Abbreviations: BPD — : bronchopulmonary dysplasia BW — : birth weight CPQCC — : California Perinatal Quality Care Collaborative GA — : gestational age gDNA — : genomic DNA GWAS — : genome-wide association study IPPV — : intermittent positive pressure ventilation NBS — : newborn screening bloodspots OR — : odds ratio PC — : principal component PMA — : postmenstrual age PNA — : postnatal age SNP — : single-nucleotide polymorphism VLBW — : very low birth weight |
| Databáze: | OpenAIRE |
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