Genome-wide association identifies novel ROP risk loci in a multiethnic cohort
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Published:2024-01-17
Issue:1
Volume:7
Page:
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ISSN:2399-3642
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Container-title:Communications Biology
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language:en
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Short-container-title:Commun Biol
Author:
Li Xiaohui, Owen Leah A.ORCID, Taylor Kent D., Ostmo Susan, Chen Yii-Der IdaORCID, Coyner Aaron S.ORCID, Sonmez Kemal, Hartnett M. Elizabeth, Guo XiuqingORCID, Ipp EliORCID, Roll Kathryn, Genter Pauline, Chan R. V. PaulORCID, DeAngelis Margaret M., Chiang Michael F.ORCID, Campbell J. PeterORCID, Rotter Jerome I.ORCID, Campbell J. Peter, Ostmo Susan, Coyner Aaron, Young Benjamin K., Kim Sang Jin, Sonmez Kemal, Schelonka Robert, Chiang Michael F., Chan R. V. Paul, Jonas Karyn, Kolli Bhavana, Horowitz Jason, Coki Osode, Eccles Cheryl-Ann, Sarna Leora, Orlin Anton, Berrocal Audina, Negron Catherin, Denser Kimberly, Cumming Kristi, Osentoski Tammy, Check Tammy, Zajechowski Mary, Lee Thomas, Nagiel Aaron, Kruger Evan, McGovern Kathryn, Contractor Dilshad, Havunjian Margaret, Simmons Charles, Murthy Raghu, Galvis Sharon, Rotter Jerome, Chen Ida, Li Xiaohui, Taylor Kent, Roll Kaye, Owen Leah, Lucci Lucia, Hartnett Mary Elizabeth, Moshfeghi Darius, Nunez Mariana, Weinberg-Smith Zac, Kalpathy-Cramer Jayashree, Erdogmus Deniz, Ioannidis Stratis, Martinez-Castellanos Maria Ana, SalinasLongoria Samantha, Romero Rafael, Arriola Andrea, Olguin-Manriquez Francisco, Meraz-Gutierrez Miroslava, Dulanto-Reinoso Carlos M., Montero-Mendoza Cristina,
Abstract
AbstractWe conducted a genome-wide association study (GWAS) in a multiethnic cohort of 920 at-risk infants for retinopathy of prematurity (ROP), a major cause of childhood blindness, identifying 1 locus at genome-wide significance level (p < 5×10-8) and 9 with significance of p < 5×10-6 for ROP ≥ stage 3. The most significant locus, rs2058019, reached genome-wide significance within the full multiethnic cohort (p = 4.96×10-9); Hispanic and European Ancestry infants driving the association. The lead single nucleotide polymorphism (SNP) falls in an intronic region within the Glioma-associated oncogene family zinc finger 3 (GLI3) gene. Relevance for GLI3 and other top-associated genes to human ocular disease was substantiated through in-silico extension analyses, genetic risk score analysis and expression profiling in human donor eye tissues. Thus, we identify a novel locus at GLI3 with relevance to retinal biology, supporting genetic susceptibilities for ROP risk with possible variability by race and ethnicity.
Funder
U.S. Department of Health & Human Services | NIH | National Eye Institute U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
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