Genome-wide association identifies novel ROP risk loci in a multiethnic cohort

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; i-ROP Consortium

doi:10.1038/s42003-023-05743-9

Genome-wide association identifies novel ROP risk loci in a multiethnic cohort

Commun Biol. 2024 Jan 17;7(1):107. doi: 10.1038/s42003-023-05743-9.

Authors

Xiaohui Li^#¹, Leah A Owen^#^{2

3

4

5}, Kent D Taylor¹, Susan Ostmo⁶, Yii-Der Ida Chen¹, Aaron S Coyner⁶, Kemal Sonmez⁶, M Elizabeth Hartnett⁷, Xiuqing Guo¹, Eli Ipp⁸, Kathryn Roll¹, Pauline Genter⁸, R V Paul Chan⁹, Margaret M DeAngelis^{1

10

11

12

13

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15}, Michael F Chiang^{16

17}, J Peter Campbell¹⁸, Jerome I Rotter¹⁹; i-ROP Consortium

Collaborators

i-ROP Consortium:
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

Affiliations

¹ Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA.
² Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT, USA. Leah.owen@hsc.utah.edu.
³ Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA. Leah.owen@hsc.utah.edu.
⁴ Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT, USA. Leah.owen@hsc.utah.edu.
⁵ Department of Ophthalmology, University at Buffalo the State University of New York, Buffalo, NY, USA. Leah.owen@hsc.utah.edu.
⁶ Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA.
⁷ Byers Eye Institute at Stanford University, Palo Alto, CA, USA.
⁸ Division of Endocrinology and Metabolism, Department of Medicine, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
⁹ Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL, USA.
¹⁰ Department of Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT, USA.
¹¹ Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA.
¹² Department of Ophthalmology, University at Buffalo the State University of New York, Buffalo, NY, USA.
¹³ Department of Biochemistry; Jacobs School of Medicine and Biomedical Sciences, University at Buffalo/State University of New York (SUNY), Buffalo, NY, USA.
¹⁴ Department of Neuroscience; Jacobs School of Medicine and Biomedical Sciences, University at Buffalo/State University of New York (SUNY), Buffalo, NY, USA.
¹⁵ Department of Genetics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo/State University of New York (SUNY), Buffalo, NY, USA.
¹⁶ National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
¹⁷ National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
¹⁸ Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA. campbelp@ohsu.edu.
¹⁹ Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation; Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA. jrotter@lundquist.org.

^# Contributed equally.

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 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.

MeSH terms

Ethnicity
Genetic Predisposition to Disease
Genome-Wide Association Study*
Humans
Infant, Newborn
Polymorphism, Single Nucleotide
Retinopathy of Prematurity*

Abstract

MeSH terms

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