FAMILIAL PRIMARY OPEN ANGLE GLAUCOMA
Principal Investigator: Janey Wiggs
Abstract: Primary open angle glaucoma (POAG) is a significant cause of blindness worldwide. Compelling evidence supports the hypothesis that specific genes influence susceptibility to the disease. The objective of this proposal is to identify POAG susceptibility genes and determine the relationships between specific genetic defects and clinical phenotype. In addition to providing insight into disease related molecular pathology, this information will lead to new treatment and diagnostic modalities. Using 103 sibpairs affected by POAG, an initial screen of the human genome has been completed, and sixteen genomic regions demonstrating initially promising linkage results have been identified. The goals of the current proposal are to confirm the initial POAG linkage results with a second set of affected pedigrees, examine candidate genes located in the confirmed regions, and identify genes that confer risk to POAG. To achieve these goals, a second pedigree set of 200 affected sibpairs will be collected and used to confirm the initial linkage results. Follow-up studies will include additional genotyping of new markers located in the regions of interest, and genotyping the initial markers in the second pedigree set. Candidate genes mapped within the confirmed genomic regions will be tested for POAG associations using both linkage analysis and family based association studies using the S-TDT. Genes that show positive associations will be screened for responsible DNA sequence alterations. Specific genetic defects will be correlated with clinical phenotype by investigating familial aggregation of clinical parameters and looking for evidence of gene/gene interactions and how these interactions may influence phenotype. Initial genome screens to identify genes responsible for two POAG risk factors, ocular hypertension (OHT) and pseudoexfoliation (PEX), will be performed.
Funding Period: 1994-12-01 - 2005-11-30
more information: NIH RePORT
- Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field lossStephanie J Loomis
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts
Ophthalmology 121:508-16. 2014..The aim of this study was to assess the association between CAV1/CAV2 single nucleotide polymorphisms (SNPs) and POAG in a large case-control dataset and to explore associations by gender and pattern of visual field (VF) loss further...
- Genome-wide association study and meta-analysis of intraocular pressureA Bilge Ozel
Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
Hum Genet 133:41-57. 2014..These results confirm the involvement of common variants in multiple genomic regions in regulating IOP and/or glaucoma risk...
- Estrogen pathway polymorphisms in relation to primary open angle glaucoma: an analysis accounting for gender from the United StatesLouis R Pasquale
Department of Ophthalmology, Mass Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA
Mol Vis 19:1471-81. 2013..We assessed the association between an estrogen metabolism single nucleotide polymorphism (SNP) panel in relation to primary open angle glaucoma (POAG), accounting for gender...
- Variations in COL15A1 and COL18A1 influence age of onset of primary open angle glaucomaJ L Wiggs
Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, MA, USA
Clin Genet 84:167-74. 2013..These results suggest genetic variation in COL15A1 and COL18A1 can modify the age of onset of both early and late onset POAG. ..
- CDKN2B-AS1 genotype-glaucoma feature correlations in primary open-angle glaucoma patients from the United StatesLouis R Pasquale
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA
Am J Ophthalmol 155:342-353.e5. 2013....
- The NEIGHBOR consortium primary open-angle glaucoma genome-wide association study: rationale, study design, and clinical variablesJaney L Wiggs
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA
J Glaucoma 22:517-25. 2013..In this report we describe the formation of the NEIGHBOR consortium, the harmonized case control definitions used for a POAG GWAS, the clinical features of the cases and controls, and the rationale for the GWAS study design. ..
- Genome-wide analysis of central corneal thickness in primary open-angle glaucoma cases in the NEIGHBOR and GLAUGEN consortiaMegan Ulmer
Duke University Center for Human Genetics, Durham, North Carolina 27710, USA
Invest Ophthalmol Vis Sci 53:4468-74. 2012....
- Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucomaJaney L Wiggs
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America
PLoS Genet 8:e1002654. 2012..009). These results suggest that neuro-protective therapies targeting TGF-beta signaling could be effective for multiple forms of glaucoma...
- Investigation of founder effects for the Thr377Met Myocilin mutation in glaucoma families from differing ethnic backgroundsAlex W Hewitt
Department of Ophthalmology, Flinders University, Adelaide, Australia
Mol Vis 13:487-92. 2007..The aim of this study was to determine if there is a common founder for the Thr377Met myocilin mutation in primary open angle glaucoma (POAG) families with various ethnic backgrounds...
- Distribution of optineurin sequence variations in an ethnically diverse population of low-tension glaucoma patients from the United StatesMichael A Hauser
Center for Human Genetics Duke School of Medicine, Harvard Medical School, Boston, MA 02114, USA
J Glaucoma 15:358-63. 2006....
- Early adult-onset POAG linked to 15q11-13 using ordered subset analysisR Rand Allingham
Duke University Eye Center and the Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710, USA
Invest Ophthalmol Vis Sci 46:2002-5. 2005..Ordered subset analysis (OSA) is a recently described method that utilizes the variability of phenotypic traits to determine underlying genetic heterogeneity...