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

  1. Author:
    McKay, G. J.
    Patterson, C. C.
    Chakravarthy, U.
    Dasari, S.
    Klaver, C. C.
    Vingerling, J. R.
    Ho, L.
    de Jong, P.
    Fletcher, A. E.
    Young, I. S.
    Sel, 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.

  2. Author Address

    [McKay, Gareth J.; Patterson, Chris C.; Young, Ian S.] Queens Univ Belfast, Royal Victoria Hosp, Ctr Publ Hlth, Belfast BT12 6BA, Antrim, North Ireland. [Chakravarthy, Usha; Dasari, Shilpa; Silvestri, Giuliana] Queens Univ Belfast, Royal Victoria Hosp, Ctr Vis & Vasc Sci, Belfast BT12 6BA, Antrim, North Ireland. [Klaver, Caroline C.] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands. [Vingerling, Johannes R.; Ho, Lintje] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [de Jong, Paulus T. V. M.] Dept Ophthalmol AMC, Amsterdam, Netherlands. [Seland, Johan H.] Univ Bergen, Stavanger Univ Hosp, Eye Dept, Stavanger, Norway. [Rahu, Mati] Natl Inst Hlth Dev, Dept Epidemiol & Biostat, Tallinn, Estonia. [Soubrane, Gisele] Univ Paris 12, Clin Ophthalmol, Paris, France. [Tomazzoli, Laura] Univ Verona, Clin Oculist, I-37100 Verona, Italy. [Topouzis, Fotis] Aristotle Univ Thessaloniki, Dept Ophthalmol, GR-54006 Thessaloniki, Greece. [Vioque, Jesus] Univ Miguel Hernandez, Dept Salud Publ, Alicante, Spain. [Vioque, Jesus] CIBERESP, Alicante, Spain. [Dean, Michael; Sawitzke, Julie] NCI, Canc & Inflammat Program, Frederick, MD 21701 USA. [Seddon, Johanna M.] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. [Seddon, Johanna M.] Tufts Med Ctr, Boston, MA USA. [Peter, Inga] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA. [Fritsche, Lars G.; Weber, Bernhard H. F.] Univ Regensburg, Inst Human Genet, Regensburg, Germany. [Keilhauer, Claudia N.] Univ Hosp Wurzburg, Dept Ophthalmol, Wurzburg, Germany. [Stambolian, Dwight; Orlin, Anton] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Gorin, Michael B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA. [Weeks, Daniel E.; Kuo, Chia-Ling] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. [Swaroop, Anand; Othman, Mohammad] Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. [Swaroop, Anand; Kanda, Atsuhiro] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA. [Chen, Wei; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Wright, Alan F.; Hayward, Caroline] Western Gen Hosp, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. [Baird, Paul N.; Guymer, Robyn H.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia. [Attia, John] Univ Newcastle, Ctr Clin Epidemiol & Biostat, Newcastle, NSW 2300, Australia. [Attia, John] John Hunter Hosp, Hunter Med Res Inst, Newcastle, NSW, Australia. [Attia, John] John Hunter Hosp, Dept Gen Med, Newcastle, NSW, Australia. [Thakkinstian, Ammarin] Mahidol Univ, Ramathibodi Hosp, Fac Med, Sect Clin Epidemiol & Biostat, Bangkok 10400, Thailand. [de Jong, Paulus T. V. M.] KNAW, Netherlands Inst Neurosci, Amsterdam, Netherlands. [Fletcher, Astrid E.] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England. [Hingorani, Aroon D.; Sofat, Reecha] UCL, Univ Ctr Clin Pharmacol, London, England. [Hingorani, Aroon D.; Sofat, Reecha] UCL, Dept Med, London, England. [Webster, Andrew R.; Moore, Anthony T.; Yates, John R. W.; Cipriani, Valentina] UCL, Inst Ophthalmol, London, England. [Webster, Andrew R.; Moore, Anthony T.; Yates, John R. W.; Cipriani, Valentina] Moorfields Eye Hosp, London, England. [Yates, John R. W.] Univ Cambridge, Dept Med Genet, Cambridge, England. [Lotery, Andrew J.] Univ Southampton, Sch Med, Clin Neurosci Div, Southampton, Hants, England. [Lotery, Andrew J.] Southampton Gen Hosp, Southampton Eye Unit, Southampton SO9 4XY, Hants, England. [Ennis, Sarah] Univ Southampton, Genet Epidemiol & Bioinformat Grp Human Genet Div, Southampton SO9 5NH, Hants, England. [Klein, Michael L.; Francis, Peter J.] Oregon Hlth & Sci Univ, Casey Eye Inst, Macular Degenerat Ctr, Portland, OR 97201 USA. [Gorin, Michael B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.;McKay, GJ (reprint author), Queens Univ Belfast, Royal Victoria Hosp, Ctr Publ Hlth, Belfast BT12 6BA, Antrim, North Ireland;g.j.mckay@qub.ac.uk
    1. Year: 2011
    2. Date: Dec
  2. Journal: Human Mutation
    1. 32
    2. 12
    3. Pages: 1407-1416
  4. Type of Article: Article
  5. ISSN: 1059-7794
  1. Abstract:

    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 APOe4 (odds ratio [OR] = 0.72 per haplotype; confidence interval [CI]: 0.650.74; P = 4.41 x 10-11) and APOe2 (OR = 1.83 for homozygote carriers; CI: 1.043.23; 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: 1.381.72; P = 2.8 x 10(-15)) and atrophic (OR = 1.38; CI: 1.181.61; P = 3.37 x 10(-5)) AMD but not early AMD (OR = 0.94; CI: 0.861.03; 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 e2 and e4 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. 32:14071416, 2011. (C) 2011 Wiley Periodicals, Inc.

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  2. DOI: 10.1002/humu.21577
  3. View record in Web of Science®
  4. WOS: 000297246800013

Library Notes

  1. Fiscal Year: FY2011-2012
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