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

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 MortensenPeter 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

Research output: Contribution to journalArticle (Academic Journal)peer-review

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.
Original languageEnglish
Pages (from-to)3028-3036
Number of pages9
JournalDiabetes
Volume64
Issue number8
DOIs
Publication statusPublished - Aug 2015

Bibliographical 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

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