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Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets.

Publication ,  Journal Article
Bailey, JNC; Gharahkhani, P; Kang, JH; Butkiewicz, M; Sullivan, DA; Weinreb, RN; Aschard, H; Allingham, RR; Ashley-Koch, A; Lee, RK; Moroi, SE ...
Published in: Invest Ophthalmol Vis Sci
February 1, 2018

PURPOSE: Sex hormones may be associated with primary open-angle glaucoma (POAG), although the mechanisms are unclear. We previously observed that gene variants involved with estrogen metabolism were collectively associated with POAG in women but not men; here we assessed gene variants related to testosterone metabolism collectively and POAG risk. METHODS: We used two datasets: one from the United States (3853 cases and 33,480 controls) and another from Australia (1155 cases and 1992 controls). Both datasets contained densely called genotypes imputed to the 1000 Genomes reference panel. We used pathway- and gene-based approaches with Pathway Analysis by Randomization Incorporating Structure (PARIS) software to assess the overall association between a panel of single nucleotide polymorphisms (SNPs) in testosterone metabolism genes and POAG. In sex-stratified analyses, we evaluated POAG overall and POAG subtypes defined by maximum IOP (high-tension [HTG] or normal tension glaucoma [NTG]). RESULTS: In the US dataset, the SNP panel was not associated with POAG (permuted P = 0.77), although there was an association in the Australian sample (permuted P = 0.018). In both datasets, the SNP panel was associated with POAG in men (permuted P ≤ 0.033) and not women (permuted P ≥ 0.42), but in gene-based analyses, there was no consistency on the main genes responsible for these findings. In both datasets, the testosterone pathway association with HTG was significant (permuted P ≤ 0.011), but again, gene-based analyses showed no consistent driver gene associations. CONCLUSIONS: Collectively, testosterone metabolism pathway SNPs were consistently associated with the high-tension subtype of POAG in two datasets.

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Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

February 1, 2018

Volume

59

Issue

2

Start / End Page

629 / 636

Location

United States

Related Subject Headings

  • Testosterone
  • Polymorphism, Single Nucleotide
  • Ophthalmology & Optometry
  • Middle Aged
  • Metabolic Networks and Pathways
  • Male
  • Low Tension Glaucoma
  • Intraocular Pressure
  • Humans
  • Glaucoma, Open-Angle
 

Citation

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ICMJE
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Bailey, J. N. C., Gharahkhani, P., Kang, J. H., Butkiewicz, M., Sullivan, D. A., Weinreb, R. N., … Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG) Consortium, . (2018). Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets. Invest Ophthalmol Vis Sci, 59(2), 629–636. https://doi.org/10.1167/iovs.17-22708
Bailey, Jessica N Cooke, Puya Gharahkhani, Jae H. Kang, Mariusz Butkiewicz, David A. Sullivan, Robert N. Weinreb, Hugues Aschard, et al. “Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets.Invest Ophthalmol Vis Sci 59, no. 2 (February 1, 2018): 629–36. https://doi.org/10.1167/iovs.17-22708.
Bailey JNC, Gharahkhani P, Kang JH, Butkiewicz M, Sullivan DA, Weinreb RN, et al. Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets. Invest Ophthalmol Vis Sci. 2018 Feb 1;59(2):629–36.
Bailey, Jessica N. Cooke, et al. “Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets.Invest Ophthalmol Vis Sci, vol. 59, no. 2, Feb. 2018, pp. 629–36. Pubmed, doi:10.1167/iovs.17-22708.
Bailey JNC, Gharahkhani P, Kang JH, Butkiewicz M, Sullivan DA, Weinreb RN, Aschard H, Allingham RR, Ashley-Koch A, Lee RK, Moroi SE, Brilliant MH, Wollstein G, Schuman JS, Fingert JH, Budenz DL, Realini T, Gaasterland T, Scott WK, Singh K, Sit AJ, Igo RP, Song YE, Hark L, Ritch R, Rhee DJ, Vollrath D, Zack DJ, Medeiros F, Vajaranant TS, Chasman DI, Christen WG, Pericak-Vance MA, Liu Y, Kraft P, Richards JE, Rosner BA, Hauser MA, Craig JE, Burdon KP, Hewitt AW, Mackey DA, Haines JL, MacGregor S, Wiggs JL, Pasquale LR, Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG) Consortium. Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets. Invest Ophthalmol Vis Sci. 2018 Feb 1;59(2):629–636.

Published In

Invest Ophthalmol Vis Sci

DOI

EISSN

1552-5783

Publication Date

February 1, 2018

Volume

59

Issue

2

Start / End Page

629 / 636

Location

United States

Related Subject Headings

  • Testosterone
  • Polymorphism, Single Nucleotide
  • Ophthalmology & Optometry
  • Middle Aged
  • Metabolic Networks and Pathways
  • Male
  • Low Tension Glaucoma
  • Intraocular Pressure
  • Humans
  • Glaucoma, Open-Angle