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",
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 mg/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.",
author = "Janine Kr{\"o}ger and Karina Meidtner and Norbert Stefan and Marcela Guevara and Kerrison, {Nicola D.} and Eva Ardanaz and Dagfinn Aune and Heiner Boeing and Miren Dorronsoro and Courtney Dow and Guy Fagherazzi and Franks, {Paul W.} and Heinz Freisling and Gunter, {Marc J.} and Huerta, {Jos{\'e} Mar{\'i}a} and Rudolf Kaaks and Key, {Timothy J.} and Khaw, {Kay Tee} and Vittorio Krogh and Tilman K{\"u}hn and Mancini, {Francesca Romana} and Amalia Mattiello and Nilsson, {Peter M.} and Anja Olsen and Kim Overvad and Domenico Palli and Quir{\'o}s, {J. Ram{\'o}n} and Olov Rolandsson and Carlotta Sacerdote and N{\'u}ria Sala and Elena Salamanca-Fern{\'a}ndez and Ivonne Sluijs and Spijkerman, {Annemieke M.W.} and Anne Tjonneland and Tsilidis, {Konstantinos K.} and Rosario Tumino and {Van Der Schouw}, {Yvonne T.} and Forouhi, {Nita G.} and Sharp, {Stephen J.} and Claudia Langenberg and Elio Riboli and Schulze, {Matthias B.} and Wareham, {Nicholas J.}",
year = "2018",
month = "6",
day = "1",
doi = "10.2337/db17-1268",
language = "English",
volume = "67",
pages = "1200--1205",
journal = "Diabetes",
issn = "1939-327X",
publisher = "American Diabetes Association Inc.",
number = "6",