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A proteogenomic signature of age-related macular degeneration in blood

A proteogenomic signature of age-related macular degeneration in blood

Title: A proteogenomic signature of age-related macular degeneration in blood
Author: Emilsson, Valur   orcid.org/0000-0001-9982-0524
Gudmundsson, Elias F
Jonmundsson, Thorarinn
Jonsson, Brynjolfur G
Twarog, Michael
Gudmundsdottir, Valborg
Li, Zhiguang
Finkel, Nancy
Poor, Stephen
Liu, Xin
... 20 more authors Show all authors
Date: 2022-06-13
Language: English
Scope: 3401
Department: Faculty of Medicine
Series: Nature Communications; 13(1)
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-022-31085-x
Subject: Augnlæknisfræði; Aged; Genetic Loci; Genome-Wide Association Study; Humans; Macular Degeneration/genetics; Mendelian Randomization Analysis; Proteogenomics; Risk Factors; Augnbotnar; Multidisciplinary; Physics and Astronomy (all); Chemistry (all); Biochemistry, Genetics and Molecular Biology (all)
URI: https://hdl.handle.net/20.500.11815/3332

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Emilsson , V , Gudmundsson , E F , Jonmundsson , T , Jonsson , B G , Twarog , M , Gudmundsdottir , V , Li , Z , Finkel , N , Poor , S , Liu , X , Esterberg , R , Zhang , Y , Jose , S , Huang , C-L , Liao , S-M , Loureiro , J , Zhang , Q , Grosskreutz , C L , Nguyen , A A , Huang , Q , Leehy , B , Pitts , R , Aspelund , T , Lamb , J R , Jonasson , F , Launer , L J , Cotch , M F , Jennings , L L , Gudnason , V & Walshe , T E 2022 , ' A proteogenomic signature of age-related macular degeneration in blood ' , Nature Communications , vol. 13 , no. 1 , 3401 , pp. 3401 . https://doi.org/10.1038/s41467-022-31085-x


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.


© 2022. The Author(s). Funding Information: The authors acknowledge the contribution of the Icelandic Heart Association (IHA) staff to the AGES-RS, as well as the involvement of all study participants. We thank the IAMDGC consortium for supplying us with their GWAS summary statistics data. National Institute on Aging (NIA) contracts N01-AG-12100 and HHSN271201200022C for V.G. financed the AGES study; retinal image collection and AMD readings were funded by the NIH Intramural Research Program (ZIAEY000401). V.G. received a funding from the NIA (1R01AG065596), and IHA received a support from Althingi (the Icelandic Parliament). The Icelandic Research Fund (IRF) funded V.E. and Va.G. with grants 195761-051, 184845-053, and 206692-051, while Va.G. received a postdoctoral research grant from the University of Iceland Research Fund Funding Information: The study was supported by the Novartis Institute for Biomedical Research. M.T., N.F., S.P., X.L., R.E., Y.Z., S.J., C.L.H., S.M.L., J.L., C.L.G., A.A.N., B.L., R.P., Z.L., L.L.J., T.E.W., Q.Z., Q.H., and J.R.L. are employees and stockholders of Novartis. All other authors have no conflict of interests to declare. Publisher Copyright: © 2022, The Author(s).

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