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[Preprint]. 2023 May 16:rs.3.rs-2855404.
doi: 10.21203/rs.3.rs-2855404/v1.

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

Jerome Rotter  1 , Xiaohui Li  2 , Leah A Owen  3 , Kent Taylor  2 , Susan Ostmo  4 , Yii-Der Ida Chen  5 , Aaron Coyner  4 , Kemal Sonmez  6 , M Elizabeth Hartnett  7 , Xiuqing Guo  2 , Eli Ipp  8 , Kathryn Roll  8 , Pauline Genter  8 , R V Paul Chan  9 , Margaret DeAngelis  10 , Michael Chiang  11 , J Peter Campbell  12
Affiliations

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

Jerome Rotter et al. Res Sq. .

Update in

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.

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Conflict of interest statement

Dr. Campbell receives research support from Genentech (San Francisco, CA). Dr. Campbell was a consultant to Boston AI Lab (Boston, MA). Dr. Chan is on the Scientific Advisory Board for Phoenix Technology Group (Pleasanton, CA), a consultant for Alcon (Ft Worth, TX). Dr. Chiang was previously a consultant for Novartis (Basel, Switzerland), and was previously an equity owner of InTeleretina, LLC (Honolulu, HI). Drs. Campbell and Chan are equity owners of Siloam Vision.

Figures

Figure 1
Figure 1. Manhattan plot of genome-wide association with ROP severity (stage 3 or greater):
Data were analyzed for all populations combined. The red line on indicates genome-wide significance (p≤ 5×10−8)
Figure 2
Figure 2. Regional association plots of top genome-wide significant SNP rs2058019 (GLI3 gene) among each ethnic group:
A: Caucasian (CA); B: African American (AA), C: Hispanic (HA), and D: all combined samples (ALL).
See this image and copyright information in PMC

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