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Abstract #108294 Published in IGR 23-4
No Strong Association between the Apolipoprotein E E4 Allele and Glaucoma: A Multicohort Study
Mullany S; Diaz-Torres S; Schmidt JM; Schmidt JM; Thomson D; Qassim A; Marshall HN; Knight LSW; Berry EC; Kolovos A; Kolovos A; Dimasi D; Lake S; Mills RA; Landers J; Mitchell P; Healey PR; Commerford T; Klebe S; Souzeau E; Hassall MM; Macgregor S; Gharahkhani P; Siggs OM; Craig JEOphthalmology science 2023; 3: 100287
PURPOSE: To elucidate a potential association between the apolipoprotein E () 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 E4 allele (death, dementia, age-related macular degeneration) and negative control outcomes not associated with the E4 allele (cataract, diabetic eye disease). Outcome phenotypes were also correlated with Alzheimer's dementia (AD), a clinical outcome highly associated with the E4 allele. MAIN OUTCOME MEASURES: Results of E4 genotype-phenotype comparisons were reported as odds ratios (ORs) with 95% confidence intervals (CIs). Replication analyses investigated E4 associations in 2 replication cohorts (CLSA and ANZRAG/BMES). RESULTS: The E4 allele was inversely associated with glaucoma (OR, 0.96; 95% CI, 0.93-0.99; = 0.016) and both negative controls (cataract: OR, 0.98; 95% CI, 0.96-0.99; = 0.015; diabetic eye disease: OR, 0.92; 95% CI, 0.87-0.97; = 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; < 0.01) and cataract (OR, 1.15; 1.04-1.28; = 0.018). No association between the E4 allele and glaucoma was observed in either replication cohort (CLSA: OR, 1.03; 95% CI, 0.89-1.19; = 0.66; ANZRAG/BMES: OR, 0.97; 95% CI, 0.84-1.12; = 0.65). CONCLUSIONS: A small negative association observed between E4 and glaucoma within the UKBB was not evident in either replication cohort and may represent an artifact of glaucoma underdiagnosis in E4 carriers. FINANCIAL DISCLOSURES: The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Department of Ophthalmology, Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia.
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