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Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies

McKay, Gareth J., Patterson, Chris C., Chakravarthy, Usha, Dasari, Shilpa, Klaver, Caroline C., Vingerling, Johannes R., Ho, Lintje, de Jong, Paulus T.V.M., Fletcher, Astrid E., Young, Ian S., Seland, Johan H., Rahu, Mati, Soubrane, Gisele, Tomazzoli, Laura, Topouzis, Fotis, Vioque, Jesus, Hingorani, Aroon D., Sofat, Reecha, Dean, Michael, Sawitzke, Julie, Seddon, Johanna M., Peter, Inga, Webster, Andrew R., Moore, Anthony T., Yates, John R.W., Cipriani, Valentina, Fritsche, Lars G., Weber, Bernhard H.F., Keilhauer, Claudia N., Lotery, Andrew J., Ennis, Sarah, Klein, Michael L., Francis, Peter J., Stambolian, Dwight, Orlin, Anton, Gorin, Michael B., Weeks, Daniel E., Kuo, Chia-Ling, Swaroop, Anand, Othman, Mohammad, Kanda, Atsuhiro, Chen, Wei, Abecasis, Goncalo R., Wright, Alan F., Hayward, Caroline, Baird, Paul N., Guymer, Robyn H., Attia, John, Thakkinstian, Ammarin and Silvestri, Giuliana (2011) Evidence of association of APOE with age-related macular degeneration - a pooled analysis of 15 studies Human Mutation, 32, (12), pp. 1407-1416. (doi:10.1002/humu.21577). (PMID:21882290).

Record type: Article


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 APO?4 (odds ratio [OR] = 0.72 per haplotype; confidence interval [CI]: 0.65–0.74; P = 4.41×10?11) and APO?2 (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 ?2 and ?4 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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Published date: December 2011
Organisations: Human Development & Health, Clinical & Experimental Sciences


Local EPrints ID: 337656
ISSN: 1059-7794
PURE UUID: edc7723b-a716-4a8f-97b6-711cc2d881c0

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Date deposited: 02 May 2012 09:04
Last modified: 18 Jul 2017 06:01

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Author: Gareth J. McKay
Author: Chris C. Patterson
Author: Usha Chakravarthy
Author: Shilpa Dasari
Author: Caroline C. Klaver
Author: Johannes R. Vingerling
Author: Lintje Ho
Author: Paulus T.V.M. de Jong
Author: Astrid E. Fletcher
Author: Ian S. Young
Author: Johan H. Seland
Author: Mati Rahu
Author: Gisele Soubrane
Author: Laura Tomazzoli
Author: Fotis Topouzis
Author: Jesus Vioque
Author: Aroon D. Hingorani
Author: Reecha Sofat
Author: Michael Dean
Author: Julie Sawitzke
Author: Johanna M. Seddon
Author: Inga Peter
Author: Andrew R. Webster
Author: Anthony T. Moore
Author: John R.W. Yates
Author: Valentina Cipriani
Author: Lars G. Fritsche
Author: Bernhard H.F. Weber
Author: Claudia N. Keilhauer
Author: Sarah Ennis
Author: Michael L. Klein
Author: Peter J. Francis
Author: Dwight Stambolian
Author: Anton Orlin
Author: Michael B. Gorin
Author: Daniel E. Weeks
Author: Chia-Ling Kuo
Author: Anand Swaroop
Author: Mohammad Othman
Author: Atsuhiro Kanda
Author: Wei Chen
Author: Goncalo R. Abecasis
Author: Alan F. Wright
Author: Caroline Hayward
Author: Paul N. Baird
Author: Robyn H. Guymer
Author: John Attia
Author: Ammarin Thakkinstian
Author: Giuliana Silvestri

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