Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies
Open accessAbstract
Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status has been reported. We present a pooled analysis (n = 21,160) demonstrating associations between late AMD and APOε4 (odds ratio [OR] = 0.72 per haplotype; confidence interval [CI]: 0.65-0.74; P = 4.41×10(-11) ) and APOε2 (OR = 1.83 for homozygote carriers; CI: 1.04-3.23; P = 0.04), following adjustment for age group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR = 1.54; CI: 1.38-1.72; P = 2.8×10(-15) ) and atrophic (OR = 1.38; CI: 1.18-1.61; P = 3.37×10(-5) ) AMD but not early AMD (OR = 0.94; CI: 0.86-1.03; P = 0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyond ε2 and ε4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology.
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Association has been demonstrated with several additional loci, each providing an entry-point into AMD biology and potential therapeutic targets.
“Association has also been demonstrated with several additional loci14–20, each providing an entry-point into AMD biology and potential therapeutic targets.”
From Seven new loci associated with age-related macular degeneration (2013) · cites this paper as [16]
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Splenic monocytes drive pathogenic subretinal inflammation in age-related macular degeneration
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The interaction effects of age, APOE and common environmental risk factors on human brain structure
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- Authors
- McKay, G. J., Patterson, C. C., Chakravarthy, U., Dasari, S., Klaver, C. C., Vingerling, J. R., Ho, L., de Jong, P. T. V. M., Fletcher, A. E., Young, I. S., Seland, J. H., Rahu, M., Soubrane, G., Tomazzoli, L., Topouzis, F., Vioque, J., Hingorani, A. D., Sofat, R., Dean, M., Sawitzke, J., Seddon, J. M., Peter, I., Webster, A. R., Moore, A. T., Yates, J. R. W., Cipriani, V., Fritsche, L. G., Weber, B. H. F., Keilhauer, C. N., Lotery, A. J., Ennis, S., Klein, M. L., Francis, P. J., Stambolian, D., Orlin, A., Gorin, M. B., Weeks, D. E., Kuo, C.-L., Swaroop, A., Othman, M., Kanda, A., Chen, W., Abecasis, G. R., Wright, A. F., Hayward, C., Baird, P. N., Guymer, R. H., Attia, J., Thakkinstian, A., & Silvestri, G.
- Affiliations
- Queen's University Belfast (GB)
- Erasmus MC (NL)
- London School of Hygiene & Tropical Medicine (GB)
- Stavanger University Hospital (NO)
- National Institute for Health Development (EE)
- University of Verona (IT)
- Aristotle University of Thessaloniki (GR)
- University College London (GB)
- National Cancer Institute (US)
- Tufts University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Moorfields Eye Hospital (GB)
- University of Cambridge (GB)
- University of Regensburg (DE)
- Augenklinik Universitätsklinikum Würzburg (DE)
- Southampton General Hospital (GB)
- University of Southampton (GB)
- Oregon Health & Science University (US)
- University of Pennsylvania (US)
- University of California, Los Angeles (US)
- University of Pittsburgh (US)
- National Institutes of Health (US)
- University of Michigan (US)
- Western General Hospital (GB)
- The University of Melbourne (AU)
- John Hunter Hospital (AU)
- Mahidol University (TH)
- Corresponding author
- McKay, Gareth J.
- ORCID
- McKay, Gareth J.
- Patterson, Chris C.
- Chakravarthy, Usha
- Klaver, Caroline C.
- Vingerling, Johannes R.
- Fletcher, Astrid E.
- Young, Ian S.
- Rahu, Mati
- Topouzis, Fotis
- Hingorani, Aroon D.
- Sofat, Reecha
- Dean, Michael
- Sawitzke, Julie
- Seddon, Johanna M.
- Webster, Andrew R.
- Moore, Anthony T.
- Yates, John R.W.
- Cipriani, Valentina
- Fritsche, Lars G.
- Weber, Bernhard H.F.
- Lotery, Andrew J.
- Ennis, Sarah
- Francis, Peter J.
- Gorin, Michael B.
- Weeks, Daniel E.
- Swaroop, Anand
- Othman, Mohammad
- Kanda, Atsuhiro
- Chen, Wei
- Hayward, Caroline
- Baird, Paul N.
- Guymer, Robyn H.
- Attia, John
- Thakkinstian, Ammarin
- Silvestri, Giuliana
- Venue
- Human Mutation
- Publisher
- Hindawi Limited
- Published
- 2011-09-12
- Volume
- 32
- Issue
- 12
- Pages
- 1407-1416
- ISSN
- 1059-7794 (ISSN-L)
- PMC
- PMC3217135
- OpenAlex
- W2030933555
- Cited by
- 151
- References
- 76
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 9 · 2023: 9 · 2022: 15 · 2021: 13 · 2020: 8 · 2019: 7 · 2018: 9 · 2017: 13 · 2016: 4 · 2015: 16 · 2014: 8 · 2013: 13 · 2012: 12
- FWCI
- 9.90
- Type
- journal article
- Language
- en
- Open access
- green
- pure.qub.ac.uk
- Licence
- Locations
- Human Mutation (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion)
- Research Portal (Queen's University Belfast) (acceptedVersion, other-oa)
- PubMed Central (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Funders
- Research to Prevent Blindness
- Tufts Medical Center
- Massachusetts Lions Eye Research Fund
- Macular Society
- National Institute for Health and Care Research (NF-SI-0507-10094)
- British Heart Foundation (RG/10/12/28456)
- European Commission
- Deutsche Forschungsgemeinschaft (WE 1259/19-1, WE1259/18-1)
- State Government of Victoria
- Moorfields Eye Hospital NHS Foundation Trust
- National Institutes of Health
- Tufts University School of Medicine
- Medical Research Council (G0000067)
- Economic and Social Research Council (ES/G007438/1)
- Japan Society for the Promotion of Science (22890007)
- National Eye Institute (ZIAEY000475, R01EY016862, R01EY011309)
- Alcon Research Institute
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- age-related macular degeneration, apolipoprotein E, APOE ε4, APOE ε2, smoking, LDL cholesterol, genetic susceptibility, neovascular AMD, atrophic AMD, early AMD, sex interaction, disease progression
- MeSH terms
- Age Factors, Aged, Apolipoproteins E, Female, Gene Frequency, Genotype, Haplotypes, Humans, Macular Degeneration, Male, Models, Genetic, Risk Factors, Sex Factors, Smoking, Case-Control Studies
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