Prediction of short-term neonatal complications in preterm infants using exome-wide genetic variation and gestational age: a pilot study
| Autor: | Irina A. Buhimschi, William C. L. Stewart, Mark A. Klebanoff, Komla M Gnona, Ben Kelly, Peter White, Leif D. Nelin |
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| Rok vydání: | 2020 |
| Předmět: |
Pediatrics
medicine.medical_specialty business.industry Gestational age behavioral disciplines and activities 03 medical and health sciences 0302 clinical medicine 030225 pediatrics mental disorders Pediatrics Perinatology and Child Health Genetic variation Post-hoc analysis Gestation Medicine Polygenic risk score business Exome 030217 neurology & neurosurgery Exome sequencing Severe complication |
| Zdroj: | Pediatric Research. 88:653-660 |
| ISSN: | 1530-0447 0031-3998 |
| Popis: | Preterm birth is the leading cause of mortality and morbidity in young children, with over a million deaths per year worldwide arising from neonatal complications (NCs). NCs are moderately heritable although the genetic causes are largely unknown. Therefore, we investigated the impact of accumulated genetic variation (burden) on NCs in non-Hispanic White (NHW) and non-Hispanic Black (NHB) preterm infants. We sequenced 182 exomes from infants with gestational ages from 26 to 31 weeks. These infants were cared for in the same time period and hospital environment. Eighty-one preterm infants did not develop NCs, whereas 101 developed at least one severe complication. We measured the effect of burden at the single-gene and exome-wide levels and derived a polygenic risk score (PRS) from the top 10 genes to predict NCs. Burden across the exome was associated with NCs in NHW (p = 0.05) preterm infants suggesting that multiple genes influence susceptibility. In a post hoc analysis, we find that PRS alone predicts NCs (AUC = 0.67) and that PRS is uncorrelated with GA ( $$\widehat {\it{\rho }}$$ = 0.05; p = 0.53). When PRS and GA at birth are combined, the AUC is 0.87. Our results support the hypothesis that genetic burden influences NCs in NHW preterm infants. |
| Databáze: | OpenAIRE |
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