Circulating fetuin - A and risk of type 2 diabetes: A mendelian randomization analysis

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Circulating fetuin - A and risk of type 2 diabetes : A mendelian randomization analysis. / Kröger, Janine; Meidtner, Karina; Stefan, Norbert; Guevara, Marcela; Kerrison, Nicola D.; Ardanaz, Eva; Aune, Dagfinn; Boeing, Heiner; Dorronsoro, Miren; Dow, Courtney; Fagherazzi, Guy; Franks, Paul W.; Freisling, Heinz; Gunter, Marc J.; Huerta, José María; Kaaks, Rudolf; Key, Timothy J.; Khaw, Kay Tee; Krogh, Vittorio; Kühn, Tilman; Mancini, Francesca Romana; Mattiello, Amalia; Nilsson, Peter M.; Olsen, Anja; Overvad, Kim; Palli, Domenico; Quirós, J. Ramón; Rolandsson, Olov; Sacerdote, Carlotta; Sala, Núria; Salamanca-Fernández, Elena; Sluijs, Ivonne; Spijkerman, Annemieke M.W.; Tjonneland, Anne; Tsilidis, Konstantinos K.; Tumino, Rosario; Van Der Schouw, Yvonne T.; Forouhi, Nita G.; Sharp, Stephen J.; Langenberg, Claudia; Riboli, Elio; Schulze, Matthias B.; Wareham, Nicholas J.

In: Diabetes, Vol. 67, No. 6, 01.06.2018, p. 1200-1205.

Research output: Contribution to journalArticle

Harvard

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 2018, 'Circulating fetuin - A and risk of type 2 diabetes: A mendelian randomization analysis', Diabetes, vol. 67, no. 6, pp. 1200-1205. https://doi.org/10.2337/db17-1268

APA

Kröger, J., Meidtner, K., Stefan, N., Guevara, M., Kerrison, N. D., Ardanaz, E., ... Wareham, N. J. (2018). Circulating fetuin - A and risk of type 2 diabetes: A mendelian randomization analysis. Diabetes, 67(6), 1200-1205. https://doi.org/10.2337/db17-1268

CBE

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. 2018. Circulating fetuin - A and risk of type 2 diabetes: A mendelian randomization analysis. Diabetes. 67(6):1200-1205. https://doi.org/10.2337/db17-1268

MLA

Vancouver

Kröger J, Meidtner K, Stefan N, Guevara M, Kerrison ND, Ardanaz E et al. Circulating fetuin - A and risk of type 2 diabetes: A mendelian randomization analysis. Diabetes. 2018 Jun 1;67(6):1200-1205. https://doi.org/10.2337/db17-1268

Author

Kröger, Janine ; Meidtner, Karina ; Stefan, Norbert ; Guevara, Marcela ; Kerrison, Nicola D. ; Ardanaz, Eva ; Aune, Dagfinn ; Boeing, Heiner ; Dorronsoro, Miren ; Dow, Courtney ; Fagherazzi, Guy ; Franks, Paul W. ; Freisling, Heinz ; Gunter, Marc J. ; Huerta, José María ; Kaaks, Rudolf ; Key, Timothy J. ; Khaw, Kay Tee ; Krogh, Vittorio ; Kühn, Tilman ; Mancini, Francesca Romana ; Mattiello, Amalia ; Nilsson, Peter M. ; Olsen, Anja ; Overvad, Kim ; Palli, Domenico ; Quirós, J. Ramón ; Rolandsson, Olov ; Sacerdote, Carlotta ; Sala, Núria ; Salamanca-Fernández, Elena ; Sluijs, Ivonne ; Spijkerman, Annemieke M.W. ; Tjonneland, Anne ; Tsilidis, Konstantinos K. ; Tumino, Rosario ; Van Der Schouw, Yvonne T. ; Forouhi, Nita G. ; Sharp, Stephen J. ; Langenberg, Claudia ; Riboli, Elio ; Schulze, Matthias B. ; Wareham, Nicholas J. / Circulating fetuin - A and risk of type 2 diabetes : A mendelian randomization analysis. In: Diabetes. 2018 ; Vol. 67, No. 6. pp. 1200-1205.

RIS

TY - JOUR

T1 - Circulating fetuin - A and risk of type 2 diabetes

T2 - Diabetes

AU - Kröger, Janine

AU - Meidtner, Karina

AU - Stefan, Norbert

AU - Guevara, Marcela

AU - Kerrison, Nicola D.

AU - Ardanaz, Eva

AU - Aune, Dagfinn

AU - Boeing, Heiner

AU - Dorronsoro, Miren

AU - Dow, Courtney

AU - Fagherazzi, Guy

AU - Franks, Paul W.

AU - Freisling, Heinz

AU - Gunter, Marc J.

AU - Huerta, José María

AU - Kaaks, Rudolf

AU - Key, Timothy J.

AU - Khaw, Kay Tee

AU - Krogh, Vittorio

AU - Kühn, Tilman

AU - Mancini, Francesca Romana

AU - Mattiello, Amalia

AU - Nilsson, Peter M.

AU - Olsen, Anja

AU - Overvad, Kim

AU - Palli, Domenico

AU - Quirós, J. Ramón

AU - Rolandsson, Olov

AU - Sacerdote, Carlotta

AU - Sala, Núria

AU - Salamanca-Fernández, Elena

AU - Sluijs, Ivonne

AU - Spijkerman, Annemieke M.W.

AU - Tjonneland, Anne

AU - Tsilidis, Konstantinos K.

AU - Tumino, Rosario

AU - Van Der Schouw, Yvonne T.

AU - Forouhi, Nita G.

AU - Sharp, Stephen J.

AU - Langenberg, Claudia

AU - Riboli, Elio

AU - Schulze, Matthias B.

AU - Wareham, Nicholas J.

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85047763125&partnerID=8YFLogxK

U2 - 10.2337/db17-1268

DO - 10.2337/db17-1268

M3 - Article

VL - 67

SP - 1200

EP - 1205

JO - Diabetes

JF - Diabetes

SN - 1939-327X

IS - 6

ER -