Circulating Protein Signatures and Causal Candidates for Type 2 Diabetes.

Szczegóły
Abstrakt

Tytuł:: Circulating Protein Signatures and Causal Candidates for Type 2 Diabetes.
Autorzy:: Gudmundsdottir V; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.; Icelandic Heart Association, Holtasmari 1, Kopavogur, Iceland.
Zaghlool SB; Department of Biophysics and Physiology, Weill Cornell Medicine - Qatar, Doha, Qatar.
Emilsson V; Icelandic Heart Association, Holtasmari 1, Kopavogur, Iceland.; Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland.
Aspelund T; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.; Icelandic Heart Association, Holtasmari 1, Kopavogur, Iceland.
Ilkov M; Icelandic Heart Association, Holtasmari 1, Kopavogur, Iceland.
Gudmundsson EF; Icelandic Heart Association, Holtasmari 1, Kopavogur, Iceland.
Jonsson SM; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
Zilhão NR; Icelandic Heart Association, Holtasmari 1, Kopavogur, Iceland.
Lamb JR; GNF Novartis, San Diego, CA.
Suhre K; Department of Biophysics and Physiology, Weill Cornell Medicine - Qatar, Doha, Qatar.
Jennings LL; Novartis Institutes for Biomedical Research, Cambridge, MA.
Gudnason V; Faculty of Medicine, University of Iceland, Reykjavik, Iceland .; Icelandic Heart Association, Holtasmari 1, Kopavogur, Iceland.
Źródło:: Diabetes [Diabetes] 2020 Aug; Vol. 69 (8), pp. 1843-1853. Date of Electronic Publication: 2020 May 08.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: Alexandria, VA : American Diabetes Association
Original Publication: [New York, American Diabetes Association]
MeSH Terms:: Diabetes Mellitus, Type 2/*genetics
Aged ; Aged, 80 and over ; Case-Control Studies ; Diabetes Mellitus, Type 2/blood ; Female ; Genetic Predisposition to Disease/genetics ; Genotype ; Humans ; Male ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide/genetics
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Grant Information:: HHSN271201200022C United States DA NIDA NIH HHS; N01AG12100 United States AG NIA NIH HHS
Molecular Sequence:: figshare 10.2337/figshare.12249884
Entry Date(s):: Date Created: 20200510 Date Completed: 20201218 Latest Revision: 20240401
Update Code:: 20240401
PubMed Central ID:: PMC7372075
DOI:: 10.2337/db19-1070
PMID:: 32385057
: Czasopismo naukowe

The increasing prevalence of type 2 diabetes poses a major challenge to societies worldwide. Blood-based factors like serum proteins are in contact with every organ in the body to mediate global homeostasis and may thus directly regulate complex processes such as aging and the development of common chronic diseases. We applied a data-driven proteomics approach, measuring serum levels of 4,137 proteins in 5,438 elderly Icelanders, and identified 536 proteins associated with prevalent and/or incident type 2 diabetes. We validated a subset of the observed associations in an independent case-control study of type 2 diabetes. These protein associations provide novel biological insights into the molecular mechanisms that are dysregulated prior to and following the onset of type 2 diabetes and can be detected in serum. A bidirectional two-sample Mendelian randomization analysis indicated that serum changes of at least 23 proteins are downstream of the disease or its genetic liability, while 15 proteins were supported as having a causal role in type 2 diabetes.
(© 2020 by the American Diabetes Association.)

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