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  • InterAct_MR_uric_acid_diabetes_third_revision_clean_version

    Rights statement: This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes in print and online at http://diabetes.diabetesjournals.org/content/64/8/3028

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A Mendelian randomization study of circulating uric acid and type 2 diabetes

Research output: Contribution to journalJournal articlepeer-review

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  • Ivonne Sluijs
  • Michael V. Holmes
  • Yvonne T. van der Schouw
  • Joline W. J. Beulens
  • Folkert W. Asselbergs
  • José María Huerta
  • Tom M. Palmer
  • Larraitz Arriola
  • Beverley Balkau
  • Aurelio Barricarte
  • Heiner Boeing
  • Françoise Clavel-Chapelon
  • Guy Fagherazzi
  • Paul W. Franks
  • Diana Gavrila
  • Rudolf Kaaks
  • Kay Tee Khaw
  • Tilman Kühn
  • Esther Molina-Montes
  • Lotte Maxild Mortensen
  • Peter M. Nilsson
  • Kim Overvad
  • Domenico Palli
  • Salvatore Panico
  • J. Ramón Quirós
  • Olov Rolandsson
  • Carlotta Sacerdote
  • Núria Sala
  • Julie A. Schmidt
  • Robert A. Scott
  • Sabina Sieri
  • Nadia Slimani
  • Annemieke Mw Spijkerman
  • Anne Tjonneland
  • Ruth C. Travis Dphil
  • Rosario Tumino
  • Daphne L. van der A
  • Stephen J. Sharp
  • Nita G. Forouhi
  • Claudia Langenberg
  • Elio Riboli
  • Nicholas J. Wareham
  • InterAct consortium
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<mark>Journal publication date</mark>08/2015
<mark>Journal</mark>Diabetes
Issue number8
Volume64
Number of pages9
Pages (from-to)3028-3036
Publication StatusPublished
Early online date27/04/15
<mark>Original language</mark>English

Abstract

We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric acid associated loci. We used data of the EPIC-InterAct case-cohort study, comprising 24,265 individuals of European ancestry from eight European countries. During a mean (SD) follow-up of 10 (4) years, 10,576 verified incident type 2 diabetes cases were ascertained. Higher uric acid associated with higher diabetes risk following adjustment for confounders, with a HR of 1.20 (95%CI: 1.11,1.30) per 59.48 µmol/L (1 mg/dL) uric acid. The genetic score raised uric acid by 17 µmol/L (95%CI: 15,18) per SD increase, and explained 4% of uric acid variation. Using the genetic score to estimate the unconfounded effect found that a 59.48 µmol/L higher uric acid concentration did not have a causal effect on diabetes (HR 1.01, 95%CI: 0.87,1.16). Including data from DIAGRAM consortium, increasing our dataset to 41,508 diabetes cases, the summary OR estimate was 0.99 (95%CI: 0.92, 1.06). In conclusion, our study does not support a causal effect of circulating uric acid on diabetes risk. Uric acid lowering therapies may therefore not be beneficial in reducing diabetes risk.

Bibliographic note

This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes in print and online at http://diabetes.diabetesjournals.org/content/64/8/3028