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

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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.
Funding Information
  • U.S. Department of Health & Human Services | NIH | National Eye Institute (RO1EY019474, R01 EY031331, R21 EY031883, 1K08EY031800-03)
  • U.S. Department of Health & Human Services | NIH | National Eye Institute
  • 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 (R01HL105756)
  • U.S. Department of Health & Human Services | NIH | National Eye Institute

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