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The effects of eight serum lipid biomarkers on age-related macular degeneration risk: a Mendelian randomization study

Citation

Han, X and Ong, J-S and Hewitt, AW and Gharahkhani, P and MacGregor, S, The effects of eight serum lipid biomarkers on age-related macular degeneration risk: a Mendelian randomization study, International Journal of Epidemiology, 50, (1) pp. 325-336. ISSN 0300-5771 (2020) [Refereed Article]

Copyright Statement

Copyright 2020 The Authors

DOI: doi:10.1093/ije/dyaa178

Abstract

Background: Age-related macular degeneration (AMD) is a leading cause of vision loss. Whereas lipids have been studied extensively to understand their effects on cardiovascular diseases, their relationship with AMD remains unclear.

Methods: Two-sample Mendelian randomization (MR) analyses were performed to systematically evaluate the causal relationships between eight serum lipid biomarkers, consisting of apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), direct low-density lipoprotein cholesterol (LDL-C), lipoprotein A [Lp(a)], triglycerides (TG) and non-HDL cholesterol (non-HDL-C), and the risk of different AMD stages and subtypes. We derived 64-407 genetic instruments for eight serum lipid biomarkers in 419 649 participants of European descent from the UK Biobank cohort. We conducted genome-wide association studies (GWAS) for 12 711 advanced AMD cases [8544 choroidal neovascularization (CNV) and 2656 geographic atrophy (GA) specific AMD subtypes] and 5336 intermediate AMD cases with 14 590 controls of European descent from the International AMD Genomics Consortium.

Results: Higher genetically predicted HDL-C and ApoA1 levels increased the risk of all AMD subtypes. LDL-C, ApoB, CHOL and non-HDL-C levels were associated with decreased risk of intermediate and GA AMD but not with CNV. Genetically predicted TG levels were associated with decreased risk of different AMD subtypes. Sensitivity analyses revealed no evidence for directional pleiotropy effects. In our multivariable MR analyses, adjusting for the effects of correlated lipid biomarkers yielded similar results.

Conclusion: These results suggest the role of lipid metabolism in drusen formation and particularly in AMD development at the early and intermediate stages. Mechanistic studies are warranted to investigate the utility of lipid pathways for therapeutic treatment in preventing AMD.

Item Details

Item Type:Refereed Article
Keywords:lipids, mendelian randomization, age-related macular degeneration, causal effect, UK Biobank
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Specific population health (excl. Indigenous health)
Objective Field:Health related to ageing
UTAS Author:Hewitt, AW (Professor Alex Hewitt)
ID Code:141856
Year Published:2020
Web of Science® Times Cited:2
Deposited By:Menzies Institute for Medical Research
Deposited On:2020-11-26
Last Modified:2021-04-07
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