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 as...

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Autores principales:	Sang Jin Kim, Kemal Sonmez, Ryan Swan, J. Peter Campbell, Susan Ostmo, R. V. Paul Chan, 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 (i-ROP) Research Consortium
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Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a378debb1fbd47f5b031410e62150d96
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spelling	oai:doaj.org-article:a378debb1fbd47f5b031410e62150d962021-12-02T13:33:45ZIdentification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes10.1038/s41598-021-83552-y2045-2322https://doaj.org/article/a378debb1fbd47f5b031410e62150d962021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83552-yhttps://doaj.org/toc/2045-2322Abstract 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.Sang Jin KimKemal SonmezRyan SwanJ. Peter CampbellSusan OstmoR. V. Paul ChanAaron NagielKimberly A. DrenserAudina M. BerrocalJason D. HorowitzXiaohui LiYii-Der Ida ChenKent D. TaylorCharles SimmonsJerome I. RotterMichael F. ChiangImaging and Informatics in Retinopathy of Prematurity (i-ROP) Research ConsortiumNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sang Jin Kim Kemal Sonmez Ryan Swan J. Peter Campbell Susan Ostmo R. V. Paul Chan 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 (i-ROP) Research Consortium Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes
description	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.
format	article
author	Sang Jin Kim Kemal Sonmez Ryan Swan J. Peter Campbell Susan Ostmo R. V. Paul Chan 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 (i-ROP) Research Consortium
author_facet	Sang Jin Kim Kemal Sonmez Ryan Swan J. Peter Campbell Susan Ostmo R. V. Paul Chan 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 (i-ROP) Research Consortium
author_sort	Sang Jin Kim
title	Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes
title_short	Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes
title_full	Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes
title_fullStr	Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes
title_full_unstemmed	Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes
title_sort	identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a378debb1fbd47f5b031410e62150d96
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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

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