No Strong Association between the Apolipoprotein E E4 Allele and Glaucoma

Sean Mullany, MD; Santiago Diaz-Torres, MPhil; Joshua M. Schmidt, PhD; Daniel Thomson, PhD; Ayub Qassim, MBBS, PhD; Henry N. Marshall, MD; Lachlan S.W. Knight, MOrth; Ella C. Berry, MChD; Antonia Kolovos, MD; David Dimasi, PhD; Stewart Lake, MBChB, PhD; Richard A. Mills, MBBS, PhD; John Landers, MBBS, PhD; Paul Mitchell, MBBS, PhD; Paul R. Healey, MBBS, PhD; Toby Commerford, MBBS; Sonja Klebe, MD, PhD; Emmanuelle Souzeau, PhD; Mark M. Hassall, MBBS, DPhil; Stuart MacGregor, PhD; Puya Gharahkhani, PhD; Owen M. Siggs, MD, DPhil; Jamie E. Craig, MBBS, DPhil

Ophthalmology Science (Sep 2023)

No Strong Association between the Apolipoprotein E E4 Allele and Glaucoma

Sean Mullany, MD,
Santiago Diaz-Torres, MPhil,
Joshua M. Schmidt, PhD,
Daniel Thomson, PhD,
Ayub Qassim, MBBS, PhD,
Henry N. Marshall, MD,
Lachlan S.W. Knight, MOrth,
Ella C. Berry, MChD,
Antonia Kolovos, MD,
David Dimasi, PhD,
Stewart Lake, MBChB, PhD,
Richard A. Mills, MBBS, PhD,
John Landers, MBBS, PhD,
Paul Mitchell, MBBS, PhD,
Paul R. Healey, MBBS, PhD,
Toby Commerford, MBBS,
Sonja Klebe, MD, PhD,
Emmanuelle Souzeau, PhD,
Mark M. Hassall, MBBS, DPhil,
Stuart MacGregor, PhD,
Puya Gharahkhani, PhD,
Owen M. Siggs, MD, DPhil,
Jamie E. Craig, MBBS, DPhil

Affiliations

Sean Mullany, MD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia; Correspondence: Sean Mullany, Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Flinders Drive, Bedford Park, Adelaide, SA 5042.
Santiago Diaz-Torres, MPhil: Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
Joshua M. Schmidt, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia
Daniel Thomson, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia
Ayub Qassim, MBBS, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia
Henry N. Marshall, MD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia
Lachlan S.W. Knight, MOrth: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia
Ella C. Berry, MChD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia
Antonia Kolovos, MD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia
David Dimasi, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia
Stewart Lake, MBChB, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia
Richard A. Mills, MBBS, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia
John Landers, MBBS, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia
Paul Mitchell, MBBS, PhD: Centre for Vision Research, University of Sydney, Sydney, Australia
Paul R. Healey, MBBS, PhD: Centre for Vision Research, University of Sydney, Sydney, Australia
Toby Commerford, MBBS: Department of Geriatric Medicine, Royal Adelaide Hospital, Adelaide, South Australia
Sonja Klebe, MD, PhD: Department of Pathology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia
Emmanuelle Souzeau, PhD: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia
Mark M. Hassall, MBBS, DPhil: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia
Stuart MacGregor, PhD: Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
Puya Gharahkhani, PhD: Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
Owen M. Siggs, MD, DPhil: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia; Garvan Institute of Medical Research, Darlinghurst, New South Wales
Jamie E. Craig, MBBS, DPhil: Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia

Journal volume & issue: Vol. 3, no. 3
p. 100287

Abstract

Read online

Purpose: To elucidate a potential association between the apolipoprotein E (APOE) E4 allele and glaucoma prevalence in large cohorts. Design: A cross-sectional analysis of baseline and prospectively collected cohort data. Participants: UK Biobank (UKBB) participants of genetically determined European ancestry (n = 438 711). Replication analyses were performed using clinical and genotyping data collected from European participants recruited to the Canadian Longitudinal Study of Aging (CLSA; n = 18 199), the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG; n = 1970), and the Blue Mountains Eye Study (BMES; n = 2440). Methods: Apolipoprotein E alleles and genotypes were determined, and their distributions were compared on the basis of glaucoma status. Similar analyses were performed using positive control outcomes associated with the APOE E4 allele (death, dementia, age-related macular degeneration) and negative control outcomes not associated with the APOE E4 allele (cataract, diabetic eye disease). Outcome phenotypes were also correlated with Alzheimer’s dementia (AD), a clinical outcome highly associated with the APOE E4 allele. Main Outcome Measures: Results of APOE E4 genotype-phenotype comparisons were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Replication analyses investigated APOE E4 associations in 2 replication cohorts (CLSA and ANZRAG/BMES). Results: The APOE E4 allele was inversely associated with glaucoma (OR, 0.96; 95% CI, 0.93–0.99; P = 0.016) and both negative controls (cataract: OR, 0.98; 95% CI, 0.96–0.99; P = 0.015; diabetic eye disease: OR, 0.92; 95% CI, 0.87–0.97; P = 0.003) in the UKBB cohort. A paradoxical positive association was observed between AD and both glaucoma (OR, 1.30; 95% CI, 1.08–1.54; P < 0.01) and cataract (OR, 1.15; 1.04–1.28; P = 0.018). No association between the APOE E4 allele and glaucoma was observed in either replication cohort (CLSA: OR, 1.03; 95% CI, 0.89–1.19; P = 0.66; ANZRAG/BMES: OR, 0.97; 95% CI, 0.84–1.12; P = 0.65). Conclusions: A small negative association observed between APOE E4 and glaucoma within the UKBB was not evident in either replication cohort and may represent an artifact of glaucoma underdiagnosis in APOE E4 carriers. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Published in Ophthalmology Science

ISSN: 2666-9145 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Ophthalmology
Website: https://www.journals.elsevier.com/ophthalmology-science/

About the journal

Abstract

Keywords