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A proteogenomic signature of age-related macular degeneration in blood

Author

Listed:
  • Valur Emilsson

    (Icelandic Heart Association
    University of Iceland)

  • Elias F. Gudmundsson

    (Icelandic Heart Association)

  • Thorarinn Jonmundsson

    (Icelandic Heart Association)

  • Brynjolfur G. Jonsson

    (Icelandic Heart Association)

  • Michael Twarog

    (Novartis Institutes for Biomedical Research)

  • Valborg Gudmundsdottir

    (Icelandic Heart Association
    University of Iceland)

  • Zhiguang Li

    (Laboratory of Epidemiology and Population Sciences, National Institute on Aging)

  • Nancy Finkel

    (Novartis Institutes for Biomedical Research)

  • Stephen Poor

    (Novartis Institutes for Biomedical Research)

  • Xin Liu

    (Novartis Institutes for Biomedical Research)

  • Robert Esterberg

    (Novartis Institutes for Biomedical Research)

  • Yiyun Zhang

    (Novartis Institutes for Biomedical Research)

  • Sandra Jose

    (Novartis Institutes for Biomedical Research)

  • Chia-Ling Huang

    (Novartis Institutes for Biomedical Research)

  • Sha-Mei Liao

    (Novartis Institutes for Biomedical Research)

  • Joseph Loureiro

    (Novartis Institutes for Biomedical Research)

  • Qin Zhang

    (Novartis Institutes for Biomedical Research)

  • Cynthia L. Grosskreutz

    (Novartis Institutes for Biomedical Research)

  • Andrew A. Nguyen

    (Novartis Institutes for Biomedical Research)

  • Qian Huang

    (Novartis Institutes for Biomedical Research)

  • Barrett Leehy

    (Novartis Institutes for Biomedical Research)

  • Rebecca Pitts

    (Novartis Institutes for Biomedical Research)

  • Thor Aspelund

    (Icelandic Heart Association)

  • John R. Lamb

    (Novartis Institutes for Biomedical Research)

  • Fridbert Jonasson

    (University of Iceland
    University Hospital)

  • Lenore J. Launer

    (Laboratory of Epidemiology and Population Sciences, National Institute on Aging)

  • Mary Frances Cotch

    (National Institutes of Health)

  • Lori L. Jennings

    (Novartis Institutes for Biomedical Research)

  • Vilmundur Gudnason

    (Icelandic Heart Association
    University of Iceland)

  • Tony E. Walshe

    (Novartis Institutes for Biomedical Research)

Abstract

Age-related macular degeneration (AMD) is one of the most common causes of visual impairment in the elderly, with a complex and still poorly understood etiology. Whole-genome association studies have discovered 34 genomic regions associated with AMD. However, the genes and cognate proteins that mediate the risk, are largely unknown. In the current study, we integrate levels of 4782 human serum proteins with all genetic risk loci for AMD in a large population-based study of the elderly, revealing many proteins and pathways linked to the disease. Serum proteins are also found to reflect AMD severity independent of genetics and predict progression from early to advanced AMD after five years in this population. A two-sample Mendelian randomization study identifies several proteins that are causally related to the disease and are directionally consistent with the observational estimates. In this work, we present a robust and unique framework for elucidating the pathobiology of AMD.

Suggested Citation

  • Valur Emilsson & Elias F. Gudmundsson & Thorarinn Jonmundsson & Brynjolfur G. Jonsson & Michael Twarog & Valborg Gudmundsdottir & Zhiguang Li & Nancy Finkel & Stephen Poor & Xin Liu & Robert Esterberg, 2022. "A proteogenomic signature of age-related macular degeneration in blood," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31085-x
    DOI: 10.1038/s41467-022-31085-x
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    References listed on IDEAS

    as
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    1. M. A. Zouache & B. T. Richards & C. M. Pappas & R. A. Anstadt & J. Liu & T. Corsetti & S. Matthews & N. A. Seager & S. Schmitz-Valckenberg & M. Fleckenstein & W. C. Hubbard & J. Thomas & J. L. Hageman, 2024. "Levels of complement factor H-related 4 protein do not influence susceptibility to age-related macular degeneration or its course of progression," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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