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Circulating Fetuin-A and risk of Type 2 Diabetes: a Mendelian randomization analysis

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Title: Circulating Fetuin-A and risk of Type 2 Diabetes: a Mendelian randomization analysis
Authors: Kröger, J
Meidtner, K
Stefan, N
Guevara, M
Kerrison, ND
Ardanaz, E
Aune, D
Boeing, H
Dorronsoro, M
Dow, C
Fagherazzi, G
Franks, PW
Freisling, H
Gunter, MJ
Huerta, JM
Kaaks, R
Key, TJ
Khaw, KT
Krogh, V
Kühn, T
Mancini, FR
Mattiello, A
Nilsson, PM
Olsen, A
Overvad, K
Palli, D
Quirós, JR
Rolandsson, O
Sacerdote, C
Sala, N
Salamanca-Fernández, E
Sluijs, I
Spijkerman, AM
Tjonneland, A
Tsilidis, KK
Tumino, R
Van der Schouw, YT
Forouhi, NG
Sharp, SJ
Langenberg, C
Riboli, E
Schulze, MB
Wareham, NJ
Item Type: Journal Article
Abstract: 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.
Issue Date: 21-May-2018
Date of Acceptance: 27-Feb-2018
URI: http://hdl.handle.net/10044/1/57866
DOI: htps://dx.doi.org/10.2337/db17-1268
ISSN: 0012-1797
Publisher: American Diabetes Association
Start Page: 1200
End Page: 1205
Journal / Book Title: Diabetes
Volume: 67
Issue: 6
Copyright Statement: © 2018 by the American Diabetes Association. http://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
Sponsor/Funder: Imperial College Trust
Funder's Grant Number: P47328
Keywords: 11 Medical And Health Sciences
Endocrinology & Metabolism
Publication Status: Published
Conference Place: United States
Online Publication Date: 2018-03-09
Appears in Collections:School of Public Health