Integrated genomic analyses in bronchopulmonary dysplasia

Abstract

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