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

Jessica N Cooke Bailey; Puya Gharahkhani; Jae H Kang; Mariusz Butkiewicz; David A Sullivan; Robert N Weinreb; Hugues Aschard; R Rand Allingham; Allison Ashley-Koch; Richard K Lee; Sayoko E Moroi; Murray H Brilliant; Gadi Wollstein; Joel S Schuman; John H Fingert; Donald L Budenz; Tony Realini; Terry Gaasterland; William K Scott; Kuldev Singh; Arthur J Sit; Robert P Igo, Jr; Yeunjoo E Song; Lisa Hark; Robert Ritch; Douglas J Rhee; Douglas Vollrath; Donald J Zack; Felipe Medeiros; Thasarat S Vajaranant; Daniel I Chasman; William G Christen; Margaret A Pericak-Vance; Yutao Liu; Peter Kraft; Julia E Richards; Bernard A Rosner; Michael A Hauser; Jamie E Craig; Kathryn P Burdon; Alex W Hewitt; David A Mackey; Jonathan L Haines; Stuart MacGregor; Janey L Wiggs; Louis R Pasquale

doi:10.1167/iovs.17-22708

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

Journal article

Open access

Peer reviewed

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

Jessica N Cooke Bailey, Puya Gharahkhani, Jae H Kang, Mariusz Butkiewicz, David A Sullivan, Robert N Weinreb, Hugues Aschard, R Rand Allingham, Allison Ashley-Koch, Richard K Lee, …

Investigative ophthalmology & visual science, Vol.59(2), pp.629-636

2018-02-01

DOI: https://doi.org/10.1167/iovs.17-22708

PMID: 29392307

Abstract

Genome-Wide Association Study

Datasets as Topic

Low Tension Glaucoma - genetics

Glaucoma, Open-Angle - genetics

Gene Frequency

Humans

Middle Aged

Intraocular Pressure - physiology

Genotype

Male

Testosterone - metabolism

Metabolic Networks and Pathways - genetics

Female

Polymorphism, Single Nucleotide

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.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.36 Ophthalmology; 1.36.226 Glaucoma
Web Of Science research areas: Ophthalmology
ESI research areas: Clinical Medicine

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Title: Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets
Creators: Jessica N Cooke Bailey - Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States
Puya Gharahkhani - Statistical Genetics, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Australia
Jae H Kang - Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
Mariusz Butkiewicz - Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States
David A Sullivan - Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
Robert N Weinreb - Department of Ophthalmology, Hamilton Glaucoma Center and Shiley Eye Institute, University of California at San Diego, La Jolla, California, United States
Hugues Aschard - Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, Massachusetts, United States
R Rand Allingham - Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, United States
Allison Ashley-Koch - Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States
Richard K Lee - Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, United States
Sayoko E Moroi - Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States
Murray H Brilliant - Center for Human Genetics, Marshfield Clinic Research Institute, Marshfield, Wisconsin, United States
Gadi Wollstein - Department of Ophthalmology, NYU Langone Medical Center, NYU School of Medicine, New York, New York, United States
Joel S Schuman - Department of Ophthalmology, NYU Langone Medical Center, NYU School of Medicine, New York, New York, United States
John H Fingert - Departments of Ophthalmology and Anatomy/Cell Biology, University of Iowa, College of Medicine, Iowa City, Iowa, United States
Donald L Budenz - Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina, United States
Tony Realini - Department of Ophthalmology, WVU Eye Institute, Morgantown, West Virginia, United States
Terry Gaasterland - Scripps Genome Center, University of California at San Diego, San Diego, California, United States
William K Scott - Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, United States
Kuldev Singh - Department of Ophthalmology, Stanford University, Palo Alto, California, United States
Arthur J Sit - Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States
Robert P Igo, Jr - Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States
Yeunjoo E Song - Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States
Lisa Hark - Wills Eye Hospital, Glaucoma Research Center, Philadelphia, Pennsylvania, United States
Robert Ritch - Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, United States
Douglas J Rhee - Department of Ophthalmology, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States
Douglas Vollrath - Department of Genetics, Stanford University, Palo Alto, California, United States
Donald J Zack - Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, Maryland, United States
Felipe Medeiros - Department of Ophthalmology, Hamilton Glaucoma Center and Shiley Eye Institute, University of California at San Diego, La Jolla, California, United States
Thasarat S Vajaranant - Department of Ophthalmology, University of Illinois College of Medicine at Chicago, Chicago, Illinois, United States
Daniel I Chasman - Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
William G Christen - Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States
Margaret A Pericak-Vance - Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, United States
Yutao Liu - Department of Cellular Biology and Anatomy, Augusta University, Augusta, Georgia, United States
Peter Kraft - Department of Biostatistics, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, Massachusetts, United States
Julia E Richards - Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, United States
Bernard A Rosner - Department of Biostatistics, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, Massachusetts, United States
Michael A Hauser - Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States
Jamie E Craig - Department of Ophthalmology, Flinders University, Adelaide, SA, Australia
Kathryn P Burdon - School of Medicine, Menzies Research Institute of Tasmania, Hobart, Australia
Alex W Hewitt - Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia
David A Mackey - Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia
Jonathan L Haines - Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States
Stuart MacGregor - Statistical Genetics, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Australia
Janey L Wiggs - Department of Ophthalmology, Mass Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
Louis R Pasquale - Department of Ophthalmology, Mass Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, United States
Publication Details: Investigative ophthalmology & visual science, Vol.59(2), pp.629-636
Publisher: United States
Grant note: R01 EY013178 / NEI NIH HHS R56 EY011671 / NEI NIH HHS P30 EY014104 / NEI NIH HHS R01 EY019126 / NEI NIH HHS R01 HL073389 / NHLBI NIH HHS R01 HL035464 / NHLBI NIH HHS R01 EY023512 / NEI NIH HHS R01 EY011671 / NEI NIH HHS R03 EY015682 / NEI NIH HHS R01 EY022305 / NEI NIH HHS R01 EY015473 / NEI NIH HHS R01 EY015543 / NEI NIH HHS R21 EY028671 / NEI NIH HHS HHSN268200782096C / NHLBI NIH HHS R01 EY008208 / NEI NIH HHS R01 EY018660 / NEI NIH HHS UL1 TR000427 / NCATS NIH HHS R01 EY015872 / NEI NIH HHS UM1 CA167552 / NCI NIH HHS R01 CA001833 / NCI NIH HHS U01 HG004608 / NHGRI NIH HHS R01 CA136725 / NCI NIH HHS U01 HG008701 / NHGRI NIH HHS U10 EY012118 / NEI NIH HHS U01 HG004446 / NHGRI NIH HHS U01 HG004728 / NHGRI NIH HHS P01 CA087969 / NCI NIH HHS R01 EY009611 / NEI NIH HHS R01 HL088521 / NHLBI NIH HHS UM1 CA186107 / NCI NIH HHS R01 EY013315 / NEI NIH HHS R01 EY009847 / NEI NIH HHS U01 HG004424 / NHGRI NIH HHS R01 HL034594 / NHLBI NIH HHS R01 CA049449 / NCI NIH HHS R01 EY010886 / NEI NIH HHS R01 EY011008 / NEI NIH HHS R01 EY009580 / NEI NIH HHS R01 EY012118 / NEI NIH HHS
Academic Unit: Miller School of Medicine; John P. Hussman Institute for Human Genomics; UMMG Department of Ophthalmology; UMMG Dept of Human Genetics - Clinical and Translational Genetics; UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation)
Language: English
Resource Type: Journal article
PMID: 29392307
Record Identifier: 991031577077502976