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dc.contributor.authorKröger, Janine
dc.contributor.authorMeidtner, Karina
dc.contributor.authorStefan, Norbert
dc.contributor.authorGuevara, Marcela
dc.contributor.authorKerrison, Nicola D
dc.contributor.authorArdanaz, Eva
dc.contributor.authorAune, Dagfinn
dc.contributor.authorBoeing, Heiner
dc.contributor.authorDorronsoro, Miren
dc.contributor.authorDow, Courtney
dc.contributor.authorFagherazzi, Guy
dc.contributor.authorFranks, Paul W
dc.contributor.authorFreisling, Heinz
dc.contributor.authorGunter, Marc J
dc.contributor.authorHuerta, José María
dc.contributor.authorKaaks, Rudolf
dc.contributor.authorKey, Timothy J
dc.contributor.authorKhaw, Kay Tee
dc.contributor.authorKrogh, Vittorio
dc.contributor.authorKühn, Tilman
dc.contributor.authorMancini, Francesca Romana
dc.contributor.authorMattiello, Amalia
dc.contributor.authorNilsson, Peter M
dc.contributor.authorOlsen, Anja
dc.contributor.authorOvervad, Kim
dc.contributor.authorPalli, Domenico
dc.contributor.authorQuirós, J Ramón
dc.contributor.authorRolandsson, Olov
dc.contributor.authorSacerdote, Carlotta
dc.contributor.authorSala, Núria
dc.contributor.authorSalamanca-Fernández, Elena
dc.contributor.authorSluijs, Ivonne
dc.contributor.authorSpijkerman, Annemieke Mw
dc.contributor.authorTjonneland, Anne
dc.contributor.authorTsilidis, Konstantinos K
dc.contributor.authorTumino, Rosario
dc.contributor.authorvan der Schouw, Yvonne T
dc.contributor.authorForouhi, Nita G
dc.contributor.authorSharp, Stephen J
dc.contributor.authorLangenberg, Claudia
dc.contributor.authorRiboli, Elio
dc.contributor.authorSchulze, Matthias B
dc.contributor.authorWareham, Nicholas J
dc.date.accessioned2018-03-22T12:01:57Z
dc.date.available2018-03-22T12:01:57Z
dc.date.issued2018-03-09
dc.identifier.citationCirculating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis. 2018 Diabetesen
dc.identifier.issn1939-327X
dc.identifier.pmid29523632
dc.identifier.doi10.2337/db17-1268
dc.identifier.urihttp://hdl.handle.net/10029/621686
dc.description.abstractFetuin-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.
dc.language.isoenen
dc.rightsArchived with thanks to Diabetesen
dc.titleCirculating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis.en
dc.typeArticleen
dc.identifier.journalDiabetes 2018; 67(6):1200-5en
html.description.abstractFetuin-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.


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