Convergence of linkage, gene expression and association data demonstrates the influence of the RAR-related orphan receptor alpha (RORA) gene on neovascular AMD: a systems biology based approach

Vision Res. 2010 Mar 31;50(7):698-715. doi: 10.1016/j.visres.2009.09.016. Epub 2009 Sep 26.


To identify novel genes and pathways associated with AMD, we performed microarray gene expression and linkage analysis which implicated the candidate gene, retinoic acid receptor-related orphan receptor alpha (RORA, 15q). Subsequent genotyping of 159 RORA single nucleotide polymorphisms (SNPs) in a family-based cohort, followed by replication in an unrelated case-control cohort, demonstrated that SNPs and haplotypes located in intron 1 were significantly associated with neovascular AMD risk in both cohorts. This is the first report demonstrating a possible role for RORA, a receptor for cholesterol, in the pathophysiology of AMD. Moreover, we found a significant interaction between RORA and the ARMS2/HTRA1 locus suggesting a novel pathway underlying AMD pathophysiology.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Cohort Studies
  • Family
  • Female
  • Gene Expression Profiling
  • Gene Frequency
  • Genetic Linkage*
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Macular Degeneration / genetics*
  • Male
  • Microarray Analysis
  • Middle Aged
  • Nuclear Receptor Subfamily 1, Group F, Member 1 / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide* / genetics


  • Nuclear Receptor Subfamily 1, Group F, Member 1
  • RORA protein, human