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.
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.
Ocular Molecular Genetics Institute and Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
Alexandra C
AC
Silveira
Margaux A
MA
Morrison
Fei
F
Ji
Haiyan
H
Xu
James B
JB
Reinecke
Scott M
SM
Adams
Trevor M
TM
Arneberg
Maria
M
Janssian
Joo-Eun
JE
Lee
Yang
Y
Yuan
Debra A
DA
Schaumberg
Maria G
MG
Kotoula
Evangeline E
EE
Tsironi
Aristoteles N
AN
Tsiloulis
Dimitrios Z
DZ
Chatzoulis
Joan W
JW
Miller
Ivana K
IK
Kim
Gregory S
GS
Hageman
Lindsay A
LA
Farrer
Neena B
NB
Haider
Margaret M
MM
DeAngelis
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D005190:Family; D005260:Female; D020869:Gene Expression Profiling; D005787:Gene Frequency; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human