RT Journal Article
A1 Bailey, Jessica N. Cooke
A1 Gharahkhani, Puya
A1 Kang, Jae H.
A1 Butkiewicz, Mariusz
A1 Sullivan, David A.
A1 Weinreb, Robert N.
A1 Aschard, Hugues
A1 Allingham, R. Rand
A1 Ashley-Koch, Allison
A1 Lee, Richard K.
A1 Moroi, Sayoko E.
A1 Brilliant, Murray H.
A1 Wollstein, Gadi
A1 Schuman, Joel S.
A1 Fingert, John H.
A1 Budenz, Donald L.
A1 Realini, Tony
A1 Gaasterland, Terry
A1 Scott, William K.
A1 Singh, Kuldev
A1 Sit, Arthur J.
A1 Igo, Robert P., Jr
A1 Song, Yeunjoo E.
A1 Hark, Lisa
A1 Ritch, Robert
A1 Rhee, Douglas J.
A1 Vollrath, Douglas
A1 Zack, Donald J.
A1 Medeiros, Felipe
A1 Vajaranant, Thasarat S.
A1 Chasman, Daniel I.
A1 Christen, William G.
A1 Pericak-Vance, Margaret A.
A1 Liu, Yutao
A1 Kraft, Peter
A1 Richards, Julia E.
A1 Rosner, Bernard A.
A1 Hauser, Michael A.
A1 Craig, Jamie E.
A1 Burdon, Kathryn P.
A1 Hewitt, Alex W.
A1 Mackey, David A.
A1 Haines, Jonathan L.
A1 MacGregor, Stuart
A1 Wiggs, Janey L.
A1 Pasquale, Louis R.
A1 for the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG) Consortium
T1 Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets
JF Investigative Ophthalmology & Visual Science
JO Invest. Ophthalmol. Vis. Sci.
YR 2018
DO 10.1167/iovs.17-22708
VO 59
IS 2
SP 629
OP 636
SN 1552-5783
AB    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.    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]).    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.    Collectively, testosterone metabolism pathway SNPs were consistently associated with the high-tension subtype of POAG in two datasets.  
RD 4/20/2021
UL https://doi.org/10.1167/iovs.17-22708