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 2020 The Authors
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 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|
|Objective Group:||Specific population health (excl. Indigenous health)|
|Objective Field:||Health related to ageing|
|UTAS Author:||Hewitt, AW (Professor Alex Hewitt)|
|Web of Science® Times Cited:||8|
|Deposited By:||Menzies Institute for Medical Research|
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