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@ARTICLE{Krger:141710,
author = {J. Kröger and K. Meidtner and N. Stefan and M. Guevara and
N. D. Kerrison and E. Ardanaz and D. Aune and H. Boeing and
M. Dorronsoro and C. Dow and G. Fagherazzi and P. W. Franks
and H. Freisling and M. J. Gunter and J. M. Huerta and R.
Kaaks$^*$ and T. J. Key and K. T. Khaw and V. Krogh and T.
Kühn$^*$ and F. R. Mancini and A. Mattiello and P. M.
Nilsson and A. Olsen and K. Overvad and D. Palli and J. R.
Quirós and O. Rolandsson and C. Sacerdote and N. Sala and
E. Salamanca-Fernández and I. Sluijs and A. M. W.
Spijkerman and A. Tjonneland and K. K. Tsilidis and R.
Tumino and Y. T. van der Schouw and N. G. Forouhi and S. J.
Sharp and C. Langenberg and E. Riboli and M. B. Schulze and
N. J. Wareham},
title = {{C}irculating {F}etuin-{A} and {R}isk of {T}ype 2
{D}iabetes: {A} {M}endelian {R}andomization {A}nalysis.},
journal = {Diabetes},
volume = {67},
number = {6},
issn = {1939-327X},
address = {Alexandria, Va},
publisher = {Assoc.},
reportid = {DKFZ-2018-01981},
pages = {1200 - 1205},
year = {2018},
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 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.},
keywords = {AHSG protein, human (NLM Chemicals) / Biomarkers (NLM
Chemicals) / alpha-2-HS-Glycoprotein (NLM Chemicals)},
cin = {C020},
ddc = {610},
cid = {I:(DE-He78)C020-20160331},
pnm = {323 - Metabolic Dysfunction as Risk Factor (POF3-323)},
pid = {G:(DE-HGF)POF3-323},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29523632},
doi = {10.2337/db17-1268},
url = {https://inrepo02.dkfz.de/record/141710},
}