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    Circulating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis.

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    Authors
    Kröger, Janine
    Meidtner, Karina
    Stefan, Norbert
    Guevara, Marcela
    Kerrison, Nicola D
    Ardanaz, Eva
    Aune, Dagfinn
    Boeing, Heiner
    Dorronsoro, Miren
    Dow, Courtney
    Fagherazzi, Guy
    Franks, Paul W
    Freisling, Heinz
    Gunter, Marc J
    Huerta, José María
    Kaaks, Rudolf
    Key, Timothy J
    Khaw, Kay Tee
    Krogh, Vittorio
    Kühn, Tilman
    Mancini, Francesca Romana
    Mattiello, Amalia
    Nilsson, Peter M
    Olsen, Anja
    Overvad, Kim
    Palli, Domenico
    Quirós, J Ramón
    Rolandsson, Olov
    Sacerdote, Carlotta
    Sala, Núria
    Salamanca-Fernández, Elena
    Sluijs, Ivonne
    Spijkerman, Annemieke Mw
    Tjonneland, Anne
    Tsilidis, Konstantinos K
    Tumino, Rosario
    van der Schouw, Yvonne T
    Forouhi, Nita G
    Sharp, Stephen J
    Langenberg, Claudia
    Riboli, Elio
    Schulze, Matthias B
    Wareham, Nicholas J
    Type
    Article
    Language
    en
    
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    Title
    Circulating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis.
    Published in
    Diabetes 2018; 67(6):1200-5
    Publiekssamenvatting
    Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. We aimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian Randomization study with SNPs located in the fetuin-A-encodingAHSGgene. We used data from eight European countries of the prospective EPIC-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 cases. A genetic score of theAHSGSNPs was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 µg/ml higher fetuin-A concentration with diabetes risk (HR 1.02 [95%-CI 0.97, 1.07]). Combining our results with those from the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 cases) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistical evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study doesn't support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.
    DOI
    10.2337/db17-1268
    PMID
    29523632
    URI
    http://hdl.handle.net/10029/621686
    ae974a485f413a2113503eed53cd6c53
    10.2337/db17-1268
    Scopus Count
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