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

Autor:	Haiyan Xu, Neena B. Haider, Joan W. Miller, Joo Eun Lee, Ivana K. Kim, Gregory S. Hageman, Maria Janssian, S. M. Adams, James B. Reinecke, Maria G Kotoula, Debra A. Schaumberg, Margaux A. Morrison, Dimitrios Z Chatzoulis, Aristoteles N. Tsiloulis, Evangeline E. Tsironi, Margaret M. DeAngelis, Trevor M. Arneberg, Alexandra C. Silveira, Lindsay A. Farrer, Fei Ji, Yang Yuan
Rok vydání:	2009
Předmět:	Male Candidate gene genetic structures Genotype Genetic Linkage Single-nucleotide polymorphism Locus (genetics) Microarray Biology RORA RAR-related orphan receptor alpha Polymerase Chain Reaction Polymorphism Single Nucleotide Article Cohort Studies Macular Degeneration Gene Frequency Humans Family Genetic Predisposition to Disease Gene Neovascularization Aged Genetics Orphan receptor Aged 80 and over Linkage Microarray analysis techniques Gene Expression Profiling Nuclear Receptor Subfamily 1 Group F Member 1 Single nucleotide polymorphisms Middle Aged Microarray Analysis Sensory Systems eye diseases Gene expression profiling Ophthalmology Haplotypes Case-Control Studies Female sense organs
Zdroj:	Vision research. 50(7)
ISSN:	1878-5646
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::deea2e371c98c1d4bc4e157844aea6da https://pubmed.ncbi.nlm.nih.gov/19786043 Zobrazit plný text záznamu Full Text from ScienceDirect