Genetic analyses of human fetal retinal pigment epithelium gene expression suggest ocular disease mechanisms

Commun Biol. 2019 May 20;2:186. doi: 10.1038/s42003-019-0430-6. eCollection 2019.


The retinal pigment epithelium (RPE) serves vital roles in ocular development and retinal homeostasis but has limited representation in large-scale functional genomics datasets. Understanding how common human genetic variants affect RPE gene expression could elucidate the sources of phenotypic variability in selected monogenic ocular diseases and pinpoint causal genes at genome-wide association study (GWAS) loci. We interrogated the genetics of gene expression of cultured human fetal RPE (fRPE) cells under two metabolic conditions and discovered hundreds of shared or condition-specific expression or splice quantitative trait loci (e/sQTLs). Co-localizations of fRPE e/sQTLs with age-related macular degeneration (AMD) and myopia GWAS data suggest new candidate genes, and mechanisms by which a common RDH5 allele contributes to both increased AMD risk and decreased myopia risk. Our study highlights the unique transcriptomic characteristics of fRPE and provides a resource to connect e/sQTLs in a critical ocular cell type to monogenic and complex eye disorders.

Keywords: Computational biology and bioinformatics; Gene expression; Macular degeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / genetics
  • Cells, Cultured
  • Chromosome Mapping
  • Energy Metabolism
  • Fetus / cytology
  • Fetus / metabolism
  • Gene Expression
  • Genetic Variation
  • Genome-Wide Association Study
  • Humans
  • Macular Degeneration / genetics
  • Myopia / genetics
  • Nonsense Mediated mRNA Decay
  • Quantitative Trait Loci
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / embryology
  • Retinal Pigment Epithelium / metabolism*
  • Risk Factors
  • Transcriptome


  • Alcohol Oxidoreductases
  • retinol dehydrogenase 5