Genetic variants associated with patent ductus arteriosus in extremely preterm infants
Dagle, J. M., Ryckman, K. K., Spracklen, C. N., Momany, A. M., Cotten, C. M., Levy, J., Page, G. P., Bell, E. F., Carlo, W. A., Shankaran, S., Goldberg, R. N., Ehrenkranz, R. A., Tyson, J. E., Stoll, B. J., Murray, J. C., & Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (2019). Genetic variants associated with patent ductus arteriosus in extremely preterm infants. Journal of Perinatology, 39(3), 401-408. Advance online publication. https://doi.org/10.1038/s41372-018-0285-6
OBJECTIVE: Patent ductus arteriosus (PDA) is a commonly observed condition in preterm infants. Prior studies have suggested a role for genetics in determining spontaneous ductal closure. Using samples from a large neonatal cohort we tested the hypothesis that common genetic variations are associated with PDA in extremely preterm infants.
STUDY DESIGN: Preterm infants (n = 1013) enrolled at NICHD Neonatal Research Network sites were phenotyped for PDA. DNA was genotyped for 1634 single nucleotide polymorphisms (SNPs) from candidate genes. Analyses were adjusted for ancestral eigenvalues and significant epidemiologic variables.
RESULTS: SNPs in several genes were associated with the clinical diagnosis of PDA and with surgical ligation in extremely preterm neonates diagnosed with PDA (p < 0.01). None of the associations were significant after correction for multiple comparisons.
CONCLUSION: We identified several common genetic variants associated with PDA. These findings may inform further studies on genetic risk factors for PDA in preterm infants.