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Ferkingstad E, Sulem P, Atlason BA, et al. Large-scale integration of the plasma proteome with genetics and disease. Nat Genet. 2021;53(12):1712-1721doi: 10.1038/s41588-021-00978-w.
Ferkingstad, E., Sulem, P., Atlason, B. A., Sveinbjornsson, G., Magnusson, M. I., Styrmisdottir, E. L., Gunnarsdottir, K., Helgason, A., Oddsson, A., Halldorsson, B. V., Jensson, B. O., Zink, F., Halldorsson, G. H., Masson, G., Arnadottir, G. A., Katrinardottir, H., Juliusson, K., Magnusson, M. K., Magnusson, O. T., Fridriksdottir, R., Saevarsdottir, S., Gudjonsson, S. A., Stacey, S. N., Rognvaldsson, S., Eiriksdottir, T., Olafsdottir, T. A., Steinthorsdottir, V., Tragante, V., Ulfarsson, M. O., Stefansson, H., Jonsdottir, I., Holm, H., Rafnar, T., Melsted, P., Saemundsdottir, J., Norddahl, G. L., Lund, S. H., Gudbjartsson, D. F., Thorsteinsdottir, U., & Stefansson, K. (2021). Large-scale integration of the plasma proteome with genetics and disease. Nature genetics, 53(12), 1712-1721. https://doi.org/10.1038/s41588-021-00978-w
Ferkingstad, Egil, et al. "Large-scale integration of the plasma proteome with genetics and disease." Nature genetics vol. 53,12 (2021): 1712-1721. doi: https://doi.org/10.1038/s41588-021-00978-w
Ferkingstad E, Sulem P, Atlason BA, Sveinbjornsson G, Magnusson MI, Styrmisdottir EL, Gunnarsdottir K, Helgason A, Oddsson A, Halldorsson BV, Jensson BO, Zink F, Halldorsson GH, Masson G, Arnadottir GA, Katrinardottir H, Juliusson K, Magnusson MK, Magnusson OT, Fridriksdottir R, Saevarsdottir S, Gudjonsson SA, Stacey SN, Rognvaldsson S, Eiriksdottir T, Olafsdottir TA, Steinthorsdottir V, Tragante V, Ulfarsson MO, Stefansson H, Jonsdottir I, Holm H, Rafnar T, Melsted P, Saemundsdottir J, Norddahl GL, Lund SH, Gudbjartsson DF, Thorsteinsdottir U, Stefansson K. Large-scale integration of the plasma proteome with genetics and disease. Nat Genet. 2021 Dec;53(12):1712-1721. doi: 10.1038/s41588-021-00978-w. Epub 2021 Dec 02. PMID: 34857953.
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Nat Genet. 2021 Dec;53(12):1712-1721. doi: 10.1038/s41588-021-00978-w. Epub 2021 Dec 02.

Large-scale integration of the plasma proteome with genetics and disease.

Nature genetics

Egil Ferkingstad, Patrick Sulem, Bjarni A Atlason, Gardar Sveinbjornsson, Magnus I Magnusson, Edda L Styrmisdottir, Kristbjorg Gunnarsdottir, Agnar Helgason, Asmundur Oddsson, Bjarni V Halldorsson, Brynjar O Jensson, Florian Zink, Gisli H Halldorsson, Gisli Masson, Gudny A Arnadottir, Hildigunnur Katrinardottir, Kristinn Juliusson, Magnus K Magnusson, Olafur Th Magnusson, Run Fridriksdottir, Saedis Saevarsdottir, Sigurjon A Gudjonsson, Simon N Stacey, Solvi Rognvaldsson, Thjodbjorg Eiriksdottir, Thorunn A Olafsdottir, Valgerdur Steinthorsdottir, Vinicius Tragante, Magnus O Ulfarsson, Hreinn Stefansson, Ingileif Jonsdottir, Hilma Holm, Thorunn Rafnar, Pall Melsted, Jona Saemundsdottir, Gudmundur L Norddahl, Sigrun H Lund, Daniel F Gudbjartsson, Unnur Thorsteinsdottir, Kari Stefansson

Affiliations

  1. deCODE genetics/Amgen, Inc., Reykjavik, Iceland.
  2. deCODE genetics/Amgen, Inc., Reykjavik, Iceland. [email protected].
  3. Department of Anthropology, University of Iceland, Reykjavik, Iceland.
  4. School of Science and Engineering, Reykjavik University, Reykjavik, Iceland.
  5. Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
  6. Faculty of Electrical and Computer Engineering, University of Iceland, Reykjavik, Iceland.
  7. School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
  8. deCODE genetics/Amgen, Inc., Reykjavik, Iceland. [email protected].
  9. Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. [email protected].

PMID: 34857953 DOI: 10.1038/s41588-021-00978-w

Abstract

The plasma proteome can help bridge the gap between the genome and diseases. Here we describe genome-wide association studies (GWASs) of plasma protein levels measured with 4,907 aptamers in 35,559 Icelanders. We found 18,084 associations between sequence variants and levels of proteins in plasma (protein quantitative trait loci; pQTL), of which 19% were with rare variants (minor allele frequency (MAF) < 1%). We tested plasma protein levels for association with 373 diseases and other traits and identified 257,490 associations. We integrated pQTL and genetic associations with diseases and other traits and found that 12% of 45,334 lead associations in the GWAS Catalog are with variants in high linkage disequilibrium with pQTL. We identified 938 genes encoding potential drug targets with variants that influence levels of possible biomarkers. Combining proteomics, genomics and transcriptomics, we provide a valuable resource that can be used to improve understanding of disease pathogenesis and to assist with drug discovery and development.

© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.

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