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The NEIGHBOR Consortium<

The NEIGHBOR (NEI Glaucoma Human genetics collaBORation) consortium is an NEI-funded collaborative effort involving 22 investigators at 12 institutions in the United States. The goal of the consortium is to identify genetic variants associated with primary open angle glaucoma (POAG) and to elucidate the molecular pathogenesis of POAG. These accomplishments would make it possible to implement effective screening and prevention strategies and to develop novel therapies.

Case and control collection: Clinical information and whole genome genotypes were collected for 2170 cases and 2347 controls. Genotyping was performed at the NIH Center for Inherited Disease Research, with support from the NEI. The clinical definition and genotyping platform were harmonized with the GLAUGEN dataset that includes another 976 cases and 1140 controls. A manuscript describing the NEIGHBOR/GLAUGEN case and control definition and overall study design is accepted for publication (The NEIGHBOR Consortium Primary Open Angle Glaucoma Genome-wide Association Study: Rationale, Study Design and Clinical Variables. Journal of Glaucoma in press, 2012).

Genome-wide association studies: The overall meta-analysis identified significant associations between two loci and POAG: the CDKN2BAS region on 9p21 (rs2157719 [G], OR=0.69 [95%CI 0.63-0.75], p = 1.86x10-18), and the SIX1/SIX6 region on chromosome 14q23 (rs10483727 [A], OR=1.32 [95%CI 1.21-1.43], p= 3.87x10-11). In sub-group analysis two loci were significantly associated with normal pressure glaucoma: 9p21 containing the CDKN2BAS gene (rs2157719 [G], OR =0.58 [95% CI 0.50-0.67], p = 1.17x10-12) and a probable regulatory region on 8q22 (rs284489 [G], OR =0.62 [95% CI 0.53-0.72], p = 8.88x10-10). These results have been accepted for publication (Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma. PLoS Genetics, in press, 2012).

Secondary analyses: A number of secondary analyses using the NEIGHBOR/GLAUGEN dataset are currently ongoing. These include identification of:

  • variants associated with central corneal thickness;
  • clinical features associated with CDKN2BAS variants;
  • molecular pathways associated with POAG;
  • variants associated with intraocular pressure;
  • copy number variants associated with POAG; and
  • variants associated with a critically important optic nerve parameter, cup-to-disc-ratio.

In addition samples collected for the GLAUGEN and NEIGHBOR studies have been included in a methylation genome-wide association study to identify genomic regions regulated through epigenetic mechanisms that are associated with POAG and in a whole-exome sequencing project to identify rare variants associated with POAG. Studies are also ongoing to identify the relationship between the chromosome 8q22 variants and cerebral spinal fluid pressure and to identify gene(s) regulated by the 8q22 region.


The NEIGHBOR Consortium Primary Open Angle Glaucoma Genome-wide Association Study: Rationale, Study design and Clinical variables. Wiggs JL, Hauser MA, Abdrabou W, Allingham RR, Budenz DL, DelBono E, Friedman DS, Kang JH, Gaasterland D, Gaasterland T, Lee RK, Lichter PR, Loomis S, Liu L, McCarty C, Medeiros FA, Moroi SE, Olson LM, Realini A, Richards JE, Rozsa FW, Schuman JS, Singh K, Stein JD, Vollrath D, Weinreb RN, Wollstein G, Yaspan BL, Yoneyama S, Zack D, Zhang K, Pericak-Vance M, Pasquale LR, Haines JL. Journal of Glaucoma, Accepted.

Common variants at 9p21 and 8q22 are associated with increased susceptibility to optic nerve degeneration in glaucoma. Wiggs JL, Yaspan BL, Hauser MA, Kang JH, Allingham RR, Olson LM, Abdrabou A, Brodeur W, Budenz DL, Caprioli J, Crenshaw A, Crooks K, DelBono E, Doheny KF, Friedman DS, Gaasterland D, Gaasterland T, Laurie C, Lee R, Lichter PR, Loomis S, Liu Yutao, Medeiros FA, McCarty C, Mirel D, Moroi SE, Musch DC, Realini A, Rozsa FW, Schuman JS, Scott K, Singh K, Stein JD, Trager EH, VanVeldhuisen P, Vollrath D, Wollstein G, Yoneyama S, Zack D, Zhang K, Richards JE, Weinreb RN, Pericak-Vance M, Pasquale LR, Haines JL. (2012) PLoS Genetics,http://www.plosgenetics.org/doi/pgen.1002654

Meeting Abstracts:

ARVO 2012:

Common Variants in 9p21 and 8q23 are associated with Normal Tension Glaucoma: Results From The NEIGHBOR and GLAUGEN Genome-wide Association Studies. Wiggs JL, Yaspan B, Kang JH, Loomis S, Pericak-Vance MA, Richards JE, Hauser MA, Haines JL, Pasquale LR, NEIGHBOR consortium investigators.

Genome-wide Analysis Of Central Corneal Thickness In POAG Cases From The NEIGHBOR Consortium. Ulmer M, Li J, Ozel AB, Richards J, Moroi SE, Yaspan B, Wiggs JL, Ashley-Koch A, NEIGHBOR Consortium Investigators, Hauser MA.

CDKN2BAS Genotype - Glaucoma Phenotype Correlations In The GLAUGEN Study And The NEIGHBOR Consortium. Pasquale LR, Loomis S, Kang JH, Yaspan B, Lee RK, Pericak-Vance MA, Hauser MA, Richards JE, Haines JL, Wiggs JL.

CDKN2BAS DNA Sequence Variants Are Associated with Exfoliation Glaucoma. FanBJ, Loomis S, Kang JH, Wang Dy, Yaspan B, Hauser MA, Pasquale LR, Haines JL, Wiggs JL, NEIGHBOR consortium investigators.

Hypothesis Independent Pathway Analysis Identifies Biologic Pathways Associated With Poag In Data From The Neighbor And Glaugen Genomewide Association Studies. Yaspan B, Pasquale LR, Loomis S, Kang JH, Pericak-Vance MA, Hauser MA, Haines JL, Wiggs JL, NEIGHBOR consortium investigators.

Parameterized Analysis of Weighted Variants in Blended Cohorts Optimizes Analysis of Exomes from Primary Open Angle Glaucoma Cases from the NEIGHBOR Study. Gaasterland T, Edsall LE, Weinreb RN, Mansouri K, Zhang K, Gaasterland DE, Hauser MA, Richards JE, Wiggs JL, NEIGHBOR Consortium Investigators.

Targeted Resequencing of CDKN2BAS Locus Identifies Variants Associated with Primary Open Angle Glaucoma. Hauser MA, Yaspan BL, Liu Y, Ashley-Koch A, Qin X, Wheeler J, Wiggs JL, Haines JL, NEIGHBOR Consortium Investigators, Allingham AA.

APAO 2012:

Results of the NEIGHBOR and GLAUGEN POAG GWAS. Wiggs, J for the NEIGHBOR GLAUGEN investigators.

ASHG 2011:

A genome-wide association study for primary open-angle glaucoma: Results from the NEIGHBOR and GLAUGEN consortia. Yaspan BL, Wiggs JL, Hauser MA, Kang JH, Olson LM, Allingham RR, Budenz DL, Chin H, Friedman DS, Gaasterland D, Gaasterland T, Laurie C, Lee RK, Lichter P, Loomis S, Liu Y, Moroi S, Realini A, Richards JE, Schuman JS, Singh K, Vollrath D, Weinreb R, Wollstein G, ZacK D, Zhang K, Pericak-Vance MA, Pasquale LR, Haines JL.

Last Updated: July 2012