@article{315e8a859c1b4845a613450f2292f5d3,
title = "Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes",
abstract = "Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease affecting premature infants. In addition to prematurity itself and oxygen treatment, genetic factors have been suggested to predispose to ROP. We aimed to identify potentially pathogenic genes and biological pathways associated with ROP by analyzing variants from whole exome sequencing (WES) data of premature infants. As part of a multicenter ROP cohort study, 100 non-Hispanic Caucasian preterm infants enriched in phenotypic extremes were subjected to WES. Gene-based testing was done on coding nonsynonymous variants. Genes showing enrichment of qualifying variants in severe ROP compared to mild or no ROP from gene-based tests with adjustment for gestational age and birth weight were selected for gene set enrichment analysis (GSEA). Mean BW of included infants with pre-plus, type-1 or type 2 ROP including aggressive posterior ROP (n = 58) and mild or no ROP (n = 42) were 744 g and 995 g, respectively. No single genes reached genome-wide significance that could account for a severe phenotype. GSEA identified two significantly associated pathways (smooth endoplasmic reticulum and vitamin C metabolism) after correction for multiple tests. WES of premature infants revealed potential pathways that may be important in the pathogenesis of ROP and in further genetic studies.",
author = "{Imaging and Informatics in Retinopathy of Prematurity (i-ROP) Research Consortium} and Kim, {Sang Jin} and Kemal Sonmez and Ryan Swan and Campbell, {J. Peter} and Susan Ostmo and Chan, {R. V.Paul} and Aaron Nagiel and Drenser, {Kimberly A.} and Berrocal, {Audina M.} and Horowitz, {Jason D.} and Xiaohui Li and Chen, {Yii Der Ida} and Taylor, {Kent D.} and Charles Simmons and Rotter, {Jerome I.} and Chiang, {Michael F.} and Chiang, {Michael F.} and Susan Ostmo and Kim, {Sang Jin} and Sonmez, {Mustafa (Kemal)} and Campbell, {J. Peter} and Chan, {R. V.Paul} and Karyn Jonas and Jason Horowitz and Osode Coki and Eccles, {Cheryl Ann} and Leora Sarna and Anton Orlin and Audina Berrocal and Catherin Negron and Kimberly Denser and Kristi Cumming and Tammy Osentoski and Tammy Check and Mary Zajechowski and Thomas Lee and Evan Kruger and Kathryn McGovern and Charles Simmons and Raghu Murthy and Sharon Galvis and Jerome Rotter and Ida Chen and Xiaohui Li and Kent Taylor and Kaye Roll and Jayashree Kalpathy-Cramer and Deniz Erdogmus and Stratis Ioannidis and Martinez-Castellanos, {Maria Ana}",
note = "Funding Information: This study was supported by Grant R01EY19474 and P30EY10572 from the National Institutes of Health (Bethesda, MD), by Grant SCH-1622679 from the National Science Foundation (Arlington, VA), and by unrestricted departmental funding from Research to Prevent Blindness (New York, NY). The provision of geno-typing data was supported in part by the National Center for Advancing Translational Sciences, CTSI Grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease diabetes Research Center (DRC) Grant DK063491 to the Southern California Diabetes Endocrinology Research Center. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s41598-021-83552-y",
language = "English (US)",
volume = "11",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}