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Testosterone pathway genetic polymorphisms in relation to primary open-angle glaucoma: an analysis in two large datasets


Cooke Bailey, JN and Gharahkhani, P and Kang, JH and Butkiewicz, M and Sullivan, DA and Weinreb, RN and Aschard, H and Allingham, RR and Ashley-Koch, A and Lee, RK and Moroi, SE and Brilliant, MH and Wollstein, G and Schuman, JS and Fingert, JH and Budenz, DL and Realini, T and Gaasterland, T and Scott, WK and Singh, K and Sit, AJ and Igo Jr, RP and Song, YE and Hark, L and Ritch, R and Rhee, DJ and Vollrath, D and Zack, DJ and Medeiros, F and Vajaranant, TS and Chasman, DI and Christen, WG and Pericak-Vance, MA and Liu, Y and Kraft, P and Richards, JE and Rosner, BA and Hauser, MA and Craig, JE and Burdon, KP and Hewitt, AW and Mackey, DA and Haines, JL and MacGregor, S and Wiggs, JL and Pasquale, LR, for the 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, Investigative Ophthalmology and Visual Science, 59, (2) pp. 629-636. ISSN 0146-0404 (2018) [Refereed Article]


Copyright Statement

2018 The Authors. Licensed under Creative Commons Attribution--NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

DOI: doi:10.1167/iovs.17-22708


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.

Item Details

Item Type:Refereed Article
Keywords:primary open-angle glaucoma, testosterone, genetics, pathway analysis
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Burdon, KP (Professor Kathryn Burdon)
UTAS Author:Mackey, DA (Professor David Mackey)
ID Code:126987
Year Published:2018
Funding Support:National Health and Medical Research Council (1059954)
Web of Science® Times Cited:9
Deposited By:Menzies Institute for Medical Research
Deposited On:2018-07-06
Last Modified:2019-02-25
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