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

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Title: A Mendelian randomization study of circulating uric acid and type 2 diabetes
Authors: Sluijs, I
Holmes, MV
Van der Schouw, YT
Beulens, JWJ
Asselbergs, FW
Maria Huerta, J
Palmer, TM
Arriola, L
Balkau, B
Barricarte, A
Boeing, H
Clavel-Chapelon, F
Fagherazzi, G
Franks, PW
Gavrila, D
Kaaks, R
Khaw, KT
Kuehn, T
Molina-Montes, E
Mortensen, LM
Nilsson, PM
Overvad, K
Palli, D
Panico, S
Ramon Quiros, J
Rolandsson, O
Sacerdote, C
Sala, N
Schmidt, JA
Scott, RA
Sieri, S
Slimani, N
Spijkerman, AMW
Tjonneland, A
Travis, RC
Tumino, R
Daphne, LVDA
Sharp, SJ
Forouhi, NG
Langenberg, C
Riboli, E
Wareham, NJ
Item Type: Journal Article
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 European Prospective Investigation into Cancer and Nutrition (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 case subjects with type 2 diabetes were ascertained. Higher uric acid was associated with a higher diabetes risk after adjustment for confounders, with a hazard ratio (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. By using the genetic score to estimate the unconfounded effect, we 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 the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) consortium, increasing our dataset to 41,508 case subjects with diabetes, the summary odds ratio 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.
Issue Date: 21-Apr-2015
Date of Acceptance: 7-Apr-2015
URI: http://hdl.handle.net/10044/1/43169
DOI: http://dx.doi.org/10.2337/db14-0742
ISSN: 0012-1797
Publisher: American Diabetes Association
Start Page: 3028
End Page: 3036
Journal / Book Title: Diabetes
Volume: 64
Issue: 8
Copyright Statement: © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Keywords: Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
ASSOCIATION ANALYSES IDENTIFY
EXCESSIVE FRUCTOSE INTAKE
METABOLIC SYNDROME
SERUM URATE
BLOOD-PRESSURE
CARDIOVASCULAR RISK
TRANSPORTER SLC2A9
NO EVIDENCE
DISEASE
INSTRUMENTS
Adult
Diabetes Mellitus, Type 2
Female
Genetic Loci
Genetic Predisposition to Disease
Humans
Male
Mendelian Randomization Analysis
Middle Aged
Prospective Studies
Uric Acid
InterAct Consortium
Humans
Diabetes Mellitus, Type 2
Genetic Predisposition to Disease
Uric Acid
Prospective Studies
Adult
Middle Aged
Female
Male
Genetic Loci
Mendelian Randomization Analysis
Endocrinology & Metabolism
11 Medical And Health Sciences
Publication Status: Published
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care



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