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

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.

197 European ancestry cases, 129 European ancestry controls, 51 African American or Afro-Caribbean cases, 60 African American or Afro-Caribbean controls, 282 Hispanic or Latin American cases, 128 Hispanic or Latin American controls, 39 Other ancestry cases, 34 Other ancestry controls