A Mendelian randomization study of circulating uric acid and type 2 diabetes.
(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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https://lup.lub.lu.se/record/5337673
- author
- organization
- publishing date
- 2015
- 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
- pmid:25918230
- ISSN
- 1939-327X
- DOI
- 10.2337/db14-0742
- language
- English
- LU publication?
- 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
- 2016-04-01 10:02:05
- date last changed
- 2022-04-19 21:54:39
@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}},
doi = {{10.2337/db14-0742}},
volume = {{64}},
year = {{2015}},
}