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Paul Franks

Paul Franks

Principal investigator

Paul Franks

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

Author

  • 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

Summary, in English

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.

Department/s

  • Genetic and Molecular Epidemiology
  • EpiHealth: Epidemiology for Health
  • Internal Medicine - Epidemiology

Publishing year

2018-06-01

Language

English

Pages

1200-1205

Publication/Series

Diabetes

Volume

67

Issue

6

Document type

Journal article

Publisher

American Diabetes Association Inc.

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genetic and Molecular Epidemiology
  • Internal Medicine - Epidemiology

ISBN/ISSN/Other

  • ISSN: 0012-1797