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Study Description

The overall goal of our research is to elucidate the pathogenesis of exfoliation syndrome and the associated glaucoma, making it possible to implement effective screening and prevention strategies and to develop novel therapies. Cases genotyped for this project are from the Nurses Health Study (NHS), the Health Professionals Follow-up Study (HPFS), the Women's Genome Health Study (WGHS), the Massachusetts Eye and Ear Infirmary (MEEI), Mayo Clinic, the University of Iowa, the University of Miami and Duke University Medical Center.

Exfoliation syndrome (XFS) is a common condition that is a major risk factor for high-tension open-angle glaucoma, pre-mature cataract formation, and increased risk of complications during cataract surgery. Previous studies suggest that exfoliation syndrome and the related glaucoma (XFG) are genetically complex, and one gene, LOXL1, has been identified as a major genetic risk factor. LOXL1 variants are found in up to 98% of affected patients; however, these same variants are also present in up to 80% of unaffected individuals, indicating that additional genetic and/or environmental factors are necessary for disease development.

Samples genotyped for this study are a case set (1,096 samples) and 24 pedigrees (98 samples). Controls for association analyses are selected from the NEIGHBORHOOD study.

  • Study Types: Case Set, Parent-Offspring
  • dbGaP estimated ancestry components using GRAF-pop
  • Number of study subjects that have individual level data available through Authorized Access: 1506

Authorized Access
Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

Study Inclusion/Exclusion Criteria

Case definition: For participants from all sites, XFS cases have clinical documentation of characteristic fibrillary material, either on the lens, pupillary ruff, anterior vitreous face, or anterior segment angle during slit biomicroscopic exam or through medical record review. Angle closure glaucoma will not be an exclusion criterion, as there is a higher risk of angle closure in patients with XFS. Our primary outcome of interest will be XFS; XFG will be considered an outcome of interest in secondary analyses. XFG will be defined by clinical evidence of both exfoliation material and glaucoma. Glaucoma status is the same definition we have used for the GLAUGEN, NEIGHBOR and NEIGHBORHOOD studies defined as: Level 1 (most likely affected with vCDR >0.7 in at least one eye, visual field defects consistent with the optic nerve examination and characteristic for glaucoma in at least one eye, and IOP >22mmHg in at least one eye); Level 2 (likely affected with 2 of three criteria listed above); Level 3 (possibly affected with one of the three criteria above) and Level 0 (no evidence of glaucoma using the criteria above). The vast majority of cases and controls are Caucasian, reflecting the populations used for this study and the fact that the disease is rarely observed in individuals of African race. Non-Caucasians identified by analysis of population substructure be analyzed separately.

Exclusion criteria: There are no exclusion criteria for exfoliation status. For glaucoma status, patients will be scored as unknown for glaucoma if they have any evidence of any other form of glaucoma, including pigmentary glaucoma or anterior segment dysgenesis. Individuals who have received chronic steroid therapy are also excluded from the analyses.

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Whole Genome Genotyping Illumina HumanHap550v3.0 561466 51468
Whole Genome Sequencing Complete Genomics Assembler Version 1.2.0; File Format Version: July 2009 N/A N/A
Whole Genome Genotyping Illumina HumanOmniExpressExome-8v1_A 951117 1059260
Study History

The cases and families genotyped for this study were supported by NIH/NEI grant R01 EY020928.

Selected publications
Diseases/Traits Related to Study (MESH terms)
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Study Attribution