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Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes.

Citation
Kim, S. J., et al. “Identification Of Candidate Genes And Pathways In Retinopathy Of Prematurity By Whole Exome Sequencing Of Preterm Infants Enriched In Phenotypic Extremes.”. Scientific Reports, p. 4966.
Center UCSD-UCLA
Author Sang Jin Kim, Kemal Sonmez, Ryan Swan, Peter Campbell, Susan Ostmo, Paul Chan V, Aaron Nagiel, Kimberly A Drenser, Audina M Berrocal, Jason D Horowitz, Xiaohui Li, Yii-Der Ida Chen, Kent D Taylor, Charles Simmons, Jerome I Rotter, Michael F Chiang, Imaging and Informatics in Retinopathy of Prematurity Research Consortium
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.

Year of Publication
2021
Journal
Scientific reports
Volume
11
Issue
1
Number of Pages
4966
Date Published
03/2021
ISSN Number
2045-2322
DOI
10.1038/s41598-021-83552-y
Alternate Journal
Sci Rep
PMID
33654115
PMCID
PMC7925531
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