%0 Journal Article
%A Kröger, Janine
%A Meidtner, Karina
%A Stefan, Norbert
%A Guevara, Marcela
%A Kerrison, Nicola D
%A Ardanaz, Eva
%A Aune, Dagfinn
%A Boeing, Heiner
%A Dorronsoro, Miren
%A Dow, Courtney
%A Fagherazzi, Guy
%A Franks, Paul W
%A Freisling, Heinz
%A Gunter, Marc J
%A Huerta, José María
%A Kaaks, Rudolf
%A Key, Timothy J
%A Khaw, Kay Tee
%A Krogh, Vittorio
%A Kühn, Tilman
%A Mancini, Francesca Romana
%A Mattiello, Amalia
%A Nilsson, Peter M
%A Olsen, Anja
%A Overvad, Kim
%A Palli, Domenico
%A Quirós, J Ramón
%A Rolandsson, Olov
%A Sacerdote, Carlotta
%A Sala, Núria
%A Salamanca-Fernández, Elena
%A Sluijs, Ivonne
%A Spijkerman, Annemieke M W
%A Tjonneland, Anne
%A Tsilidis, Konstantinos K
%A Tumino, Rosario
%A van der Schouw, Yvonne T
%A Forouhi, Nita G
%A Sharp, Stephen J
%A Langenberg, Claudia
%A Riboli, Elio
%A Schulze, Matthias B
%A Wareham, Nicholas J
%T Circulating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis.
%D 2018
%U http://hdl.handle.net/10668/12223
%X 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 single nucleotide polymorphisms located in the fetuin-A-encoding AHSG gene. We used data from eight European countries of the European Prospective Investigation into Cancer and Nutrition (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 case subjects. A genetic score of the AHSG single nucleotide polymorphisms 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 (hazard ratio 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 case subjects) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistic evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study does not support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.
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