Background and aims Bronchopulmonary dysplasia (BPD) is the most common chronic disease associated with very preterm birth. BPD has a significant genetic background but the predisposing genes are insufficiently known. The aim is to find genetic factors that predispose to moderate-severe BPD using a hypothesis-free, genome-wide approach.
Methods The study populations included preterm infants (gestational age <31 weeks) born during 1997–2013 in Oulu University Hospital and during 2010–2013 in other Finnish University Hospitals (Helsinki, K uopio, Tampere, Turku). DNA samples were genotyped using the Illumina HumanCoreExome BeadChip consisting of approximately 550,000 single-nucleotide polymorphisms (SNPs); after quality control, 60 cases (moderate-severe BPD) and 114 controls (no or mild BPD) remained for a genome-wide association study (GWAS). In the next step, approximately 200 SNPs showing suggestive signals are genotyped in additional infants (n = 116/232) to determine which associations are replicated.
Results In GWAS, we detected suggestive association signals (p < 1–4) for several SNPs; many of these SNPs were located within or near genes that can be considered as plausible candidate genes for BPD (e.g. the CRP and PTPN6 genes encoding C-reactive protein and protein-tyrosine phosphatase SHP-1, respectively). Some of the SNPs showing suggestive associations in two previous GWASs of BPD showed weak associations (e.g. those within the PALM2 and CTNNA3 genes).
Conclusions In genome-wide association study of BPD, we detected several suggestive associations. These initial results require verification in subsequent studies, including replication in additional populations and functional studies of the arising candidate genes.
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