| 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, AMW; Tjonneland, A; Tsilidis, KK; Tumino, R; Van Der Schouw, YT; Forouhi, NG; Sharp, SJ; Langenberg, C; Riboli, E; Schulze, MB; Wareham, NJ |
| Publisher Information: |
American Diabetes Association |
| Publication Year: |
2019 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.2337/db17-1268 |
| Availability: |
https://doi.org/10.2337/db17-1268; https://ora.ox.ac.uk/objects/uuid:3c2831b6-f575-4ae2-ab17-0f3984e34ae9 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.9363A80E |
| Database: |
BASE |