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

Sluijs, Ivonne; Holmes, Michael V; van der Schouw, Yvonne T; Beulens, Joline Wj; Asselbergs, Folkert W; Huerta, José María; Palmer, Tom M; Arriola, Larraitz; Balkau, Beverley and Barricarte, Aurelio, et al. (2015) In Diabetes 64(8). p.3028-3036
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... (More)
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. (Less)
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type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
64
issue
8
pages
3028 - 3036
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:25918230
  • wos:000358671300040
  • scopus:84943357645
ISSN
1939-327X
DOI
10.2337/db14-0742
language
English
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yes
id
8356db82-f452-440f-bb42-c3f122cf483d (old id 5337673)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25918230?dopt=Abstract
date added to LUP
2015-05-01 22:13:59
date last changed
2017-10-29 03:04:08
@article{8356db82-f452-440f-bb42-c3f122cf483d,
  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.},
  author       = {Sluijs, Ivonne and Holmes, Michael V and van der Schouw, Yvonne T and Beulens, Joline Wj and Asselbergs, Folkert W and Huerta, José María and Palmer, Tom M and Arriola, Larraitz and Balkau, Beverley and Barricarte, Aurelio and Boeing, Heiner and Clavel-Chapelon, Françoise and Fagherazzi, Guy and Franks, Paul and Gavrila, Diana and Kaaks, Rudolf and Khaw, Kay Tee and Kühn, Tilman and Molina-Montes, Esther and Mortensen, Lotte Maxild and Nilsson, Peter and Overvad, Kim and Palli, Domenico and Panico, Salvatore and Quirós, J Ramón and Rolandsson, Olov and Sacerdote, Carlotta and Sala, Núria and Schmidt, Julie A and Scott, Robert A and Sieri, Sabina and Slimani, Nadia and Spijkerman, Annemieke Mw and Tjonneland, Anne and Travis Dphil, Ruth C and Tumino, Rosario and van der A, Daphne L and Sharp, Stephen J and Forouhi, Nita G and Langenberg, Claudia and Riboli, Elio and Wareham, Nicholas J},
  issn         = {1939-327X},
  language     = {eng},
  number       = {8},
  pages        = {3028--3036},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {A Mendelian randomization study of circulating uric acid and type 2 diabetes.},
  url          = {http://dx.doi.org/10.2337/db14-0742},
  volume       = {64},
  year         = {2015},
}