Title |
Circulating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis
|
---|---|
Published in |
Diabetes, March 2018
|
DOI | 10.2337/db17-1268 |
Pubmed ID | |
Authors |
Janine Kröger, Karina Meidtner, Norbert Stefan, Marcela Guevara, Nicola D Kerrison, Eva Ardanaz, Dagfinn Aune, Heiner Boeing, Miren Dorronsoro, Courtney Dow, Guy Fagherazzi, Paul W Franks, Heinz Freisling, Marc J Gunter, José María Huerta, Rudolf Kaaks, Timothy J Key, Kay Tee Khaw, Vittorio Krogh, Tilman Kühn, Francesca Romana Mancini, Amalia Mattiello, Peter M Nilsson, Anja Olsen, Kim Overvad, Domenico Palli, J Ramón Quirós, Olov Rolandsson, Carlotta Sacerdote, Núria Sala, Elena Salamanca-Fernández, Ivonne Sluijs, Annemieke M W Spijkerman, Anne Tjonneland, Konstantinos K Tsilidis, Rosario Tumino, Yvonne T van der Schouw, Nita G Forouhi, Stephen J Sharp, Claudia Langenberg, Elio Riboli, Matthias B Schulze, Nicholas J Wareham |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | 38% |
Canada | 2 | 25% |
United Kingdom | 2 | 25% |
Spain | 1 | 13% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 5 | 63% |
Scientists | 3 | 38% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 72 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 17 | 24% |
Student > Master | 8 | 11% |
Student > Bachelor | 8 | 11% |
Student > Ph. D. Student | 6 | 8% |
Student > Doctoral Student | 5 | 7% |
Other | 12 | 17% |
Unknown | 16 | 22% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 21 | 29% |
Nursing and Health Professions | 10 | 14% |
Biochemistry, Genetics and Molecular Biology | 7 | 10% |
Agricultural and Biological Sciences | 4 | 6% |
Business, Management and Accounting | 2 | 3% |
Other | 7 | 10% |
Unknown | 21 | 29% |