Year: 2024
Type: article
Study design: Observational Study
Abstract: We 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 2 loci at genome-wide significance level (p<5×10-8) and 7 at suggestive significance (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 Caucasian 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 report the largest ROP GWAS to date, identifying a novel locus at GLI3 with relevance to retinal biology supporting genetic susceptibilities for ROP risk with possible variability by race and ethnicity.
Source: Communications Biology
Authors: Xiaohui Li, Leah A. Owen, Kent D. Taylor, Susan Ostmo, Yii-Der Ida Chen, Aaron S. Coyner, Kemal Sonmez, M. Elizabeth Hartnett, Xiuqing Guo, Eli Ipp, Kathryn Roll, Pauline Genter, R. V. Paul Chan, Margaret M. DeAngelis, Michael F. Chiang, J. Peter Campbell, Jerome I. Rotter, J. Peter Campbell, Susan Ostmo, Aaron Coyner, Benjamin K. Young, Sang Jin Kim, Kemal Sonmez, Robert Schelonka, Michael F. Chiang, R. V. Paul Chan, Karyn Jonas, Bhavana Kolli, Jason Horowitz, Osode Coki, Cheryl-Ann Eccles, Leora Sarna, Anton Orlin, Audina Berrocal, Catherin Negron, Kimberly Denser, Kristi Cumming, Tammy Osentoski, Tammy Check, Mary Zajechowski, Thomas Lee, Aaron Nagiel, Evan Kruger, Kathryn McGovern, Dilshad Contractor, Margaret Havunjian, Charles Simmons, Raghu Murthy, Sharon Galvis, Jerome Rotter, Ida Chen, Xiaohui Li, Kent Taylor, Kaye Roll, Leah Owen, Lucia Lucci, Mary Elizabeth Hartnett, Darius Moshfeghi, Mariana Nunez, Zac Weinberg-Smith, Jayashree Kalpathy-Cramer, Deniz Erdogmus, Stratis Ioannidis, Maria Ana Martinez-Castellanos, Samantha SalinasLongoria, Rafael Romero, Andrea Arriola, Francisco Olguin-Manriquez, Miroslava Meraz-Gutierrez, Carlos M. Dulanto-Reinoso, Cristina Montero-Mendoza
Institutions: The Lundquist Institute, Harbor–UCLA Medical Center, University of Utah, University at Buffalo, State University of New York, Oregon Health & Science University, Stanford University, University of Illinois Chicago, National Institutes of Health, United States National Library of Medicine, National Eye Institute, Columbia University, Weill Cornell Medicine, Corewell Health William Beaumont University Hospital, Children's Hospital Los Angeles, Cedars-Sinai Medical Center, Massachusetts General Hospital, Northeastern University, Asociacion Para Evitar la Ceguera en México Hospital Dr. Luis Sánchez Bulnes
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,890
Funders: U.S. Department of Health and Human Services, United States Agency for International Development, Research to Prevent Blindness, Seva Foundation, National Institutes of Health, Genentech, National Heart, Lung, and Blood Institute, National Eye Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: G1028935811, Robust AI to develop risk models in retinopathy of prematurity using deep learning, Clinical and genetic analysis of retinopathy of prematurity, A Phase 2 Study of the Value of Pre-symptomatic Genetic Risk Assessment for Age-Related Macular Degeneration, G2631738854, G2682896438, Systems-Biology Analysis of Mechanisms Informing Preeclampsia-Mediated ROP Protection, G3540319771, G3692229207, G4171837440, G4745162879, G5399686822, G5674025686, Genetics of Diabetic Retinopathy in Hispanics, CHARGE consortium: omics discovery for CVD and aging phenotypes, Artificial intelligence assisted panoramic Optical Coherence Tomography Angiography for Retinopathy of Prematurity, G7772809986, G7938937539, G8522611149, G8722294186, G9000124170, G9000140433, G9000264003, Mechanisms of Angiogenesis in ROP, Diabetes Research Center (DRC), University of Utah Core Vision Research Grant, Ophthalmology Core Facility, UCLA Clinical and Translational Science Institute
OpenAlex ID: W4390941819