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NEI Statement

National Eye Institute
National Institutes of Health

NEI Initiatives on Glaucoma

March 2010

• NEI Glaucoma Human Genetics Collaboration (NEIGHBOR)
• Gene-Environment Interactions in Glaucoma (GLAUGEN) Research Consortium

In 2008, NIH established the NEI Glaucoma Human genetic collaboration (NEIGHBOR), a consortium of clinicians and geneticists who will ultimately contribute data from more than 4000 individuals (2000 primary open-angle glaucoma cases and 2000 controls). The NEIGHBOR consortium consists of 22 investigators at 12 institutions throughout the United States. The consortium investigators will use harmonized clinical definitions for glaucoma phenotypes and the identical genotyping technology platform thereby increasing the statistical power for discovering genetic factors associated with glaucoma.

Establishment of the NEIGHBOR infrastructure is resource-intensive, particularly in ascertaining and phenotyping primary open-angle glaucoma (POAG) patients and carefully matched control subjects, collecting and genotyping their DNA, and then applying state-of-the-art analysis methods. American Recovery and Reinvestment Act (ARRA) funds support and extend the unique, timely scientific opportunities afforded by NEIGHBOR studies. The funds accelerate NEIGHBOR's efforts both to coordinate the collection and preparation of DNA samples for genotyping and for collecting clinical phenotypes.

In parallel with NEIGHBOR, the GLAUGEN consortium (Gene-Environment interactions in glaucoma) will collect data from 2400 individuals (1200 POAG cases and 1200 controls). The GLAUGEN consortium is a component of the NIH Gene-Environment Initiative (GEI) established to identify the relationships of environmental exposures to gene-trait associations in common, complex diseases. NEIGHBOR and GLAUGEN are using standardized definitions for glaucoma that will enable researchers to combine data across the consortia. Together, these two consortia will initiate large-scale, genome wide association studies (GWAS) for identifying genetic variants associated with POAG, as well as many gene-gene, and gene-environment interactions.

The success of GWAS in discovering genes for POAG depends on multiple factors including the study design, the careful harmonization of phenotype definitions, the appropriateness of control subjects, and the sample size employed in the study. Although previous GWAS identified a few genetic loci important for POAG, much larger collaborative studies are required to have sufficient statistical power to identify the disease causing genes. Furthermore, genetic variations identified by one GWAS study need to be replicated and validated in separate and distinct study populations. The combined analysis of GLAUGEN and NEIGHBOR GWAS scans will likely to lead to the identification of novel genetic variations associated with POAG.

ARRA also provides funds for important new studies of POAG that leverage the existing NEIGHBOR and GLAUGEN data by subjecting carefully selected subsets of these samples to further analysis that enhances and extends the single nucleotide polymorphism (SNP)-based GWAS. The proposed gene resequencing uses the new, cutting edge technologies of genome sequence capture methods and high throughput sequencing to discover POAG-associated regulatory variants residing within the protein-coding exons as well as flanking introns. Gene resequencing will begin with samples from 200 POAG patients and 200 control subjects.

Last Reviewed: March 2010