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Variation in complement factor 3 is associated with risk of age-related macular degeneration

Nature Genetics volume 39, pages 12001201 (2007) | Download Citation

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Abstract

The association of variants in complement factors H and B with age-related macular degeneration has led to more intense genetic and functional analysis of the complement pathway. We identify a nonsynonymous coding change in complement factor 3 that is strongly associated with risk of age-related macular degeneration in a large case-control sample.

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Acknowledgements

We thank the participants, their families and numerous ophthalmologists throughout the country who participated in this study. We particularly thank D. Mirel and the National Center for Research Resources Broad Institute Center for Genotyping and Analysis for expert design and execution of the SNP genotyping reported herein. We also thank AREDS participants and investigators and the EMMES Corporation for their work on the AREDS Genetic Repository. Funding support for AREDS was provided by the National Eye Institute (N01-EY-0-2127). This research was supported by the NIH (grant EY11309); the Foundation Fighting Blindness; the Massachusetts Lions Research Fund; the Macular Degeneration Research Fund of the Ophthalmic Epidemiology and Genetics Service, the New England Eye Center, Tufts-New England Medical Center; and the Broad Institute Center for Genotyping and Analysis (through grant U54 RR020278 from the National Center for Research Resources).

Author information

Affiliations

  1. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

    • Julian B Maller
    • , Jesen A Fagerness
    • , Benjamin M Neale
    •  & Mark J Daly
  2. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.

    • Julian B Maller
    • , Jesen A Fagerness
    • , Benjamin M Neale
    •  & Mark J Daly
  3. Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts-New England Medical Center, 750 Washington St. #450, Boston, Massachusetts 02111, USA.

    • Robyn C Reynolds
    •  & Johanna M Seddon
  4. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London SE5 8AP, UK.

    • Benjamin M Neale
  5. Harvard Medical School, Boston, Massachusetts 02115, USA.

    • Mark J Daly

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Contributions

J.M.S. and R.C.R. collected clinical information. J.M.S. obtained the funding and samples and is an AREDS co-investigator. J.B.M. and J.A.F. analyzed the data with contributions from B.M.N., under the supervision of M.J.D. J.B.M., M.J.D. and J.M.S. wrote the paper with contributions from J.A.F. M.J.D. and J.M.S. jointly supervised this study.

Corresponding authors

Correspondence to Mark J Daly or Johanna M Seddon.

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    Supplementary Tables 1–2, Supplementary Methods

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DOI

https://doi.org/10.1038/ng2131

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