TY - JOUR
T1 - A Mendelian randomization study of circulating uric acid and type 2 diabetes
AU - Sluijs, Ivonne
AU - Holmes, Michael V.
AU - van der Schouw, Yvonne T.
AU - Beulens, Joline W. J.
AU - Asselbergs, Folkert W.
AU - Huerta, José María
AU - Palmer, Tom M.
AU - Arriola, Larraitz
AU - Balkau, Beverley
AU - Barricarte, Aurelio
AU - Boeing, Heiner
AU - Clavel-Chapelon, Françoise
AU - Fagherazzi, Guy
AU - Franks, Paul W.
AU - Gavrila, Diana
AU - Kaaks, Rudolf
AU - Khaw, Kay Tee
AU - Kühn, Tilman
AU - Molina-Montes, Esther
AU - Mortensen, Lotte Maxild
AU - Nilsson, Peter M.
AU - Overvad, Kim
AU - Palli, Domenico
AU - Panico, Salvatore
AU - Quirós, J. Ramón
AU - Rolandsson, Olov
AU - Sacerdote, Carlotta
AU - Sala, N. ria
AU - Schmidt, Julie A.
AU - Scott, Robert A.
AU - Sieri, Sabina
AU - Slimani, Nadia
AU - Spijkerman, Annemieke M. W.
AU - Tjonneland, Anne
AU - Travis, Ruth C.
AU - Tumino, Rosario
AU - van der Daphne, L. A.
AU - Sharp, Stephen J.
AU - Forouhi, Nita G.
AU - Langenberg, Claudia
AU - Riboli, Elio
AU - Wareham, Nicholas J.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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 mmol/L (1 mg/dL) uric acid. The genetic score raised uric acid by 17 |xmol/L (95% CI15,18) 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 n-mol/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 Metaanalysis (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.
AB - 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 mmol/L (1 mg/dL) uric acid. The genetic score raised uric acid by 17 |xmol/L (95% CI15,18) 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 n-mol/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 Metaanalysis (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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84943357645&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/25918230
UR - http://www.scopus.com/inward/record.url?scp=84943357645&partnerID=8YFLogxK
U2 - https://doi.org/10.2337/db14-0742
DO - https://doi.org/10.2337/db14-0742
M3 - Article
C2 - 25918230
SN - 0012-1797
VL - 64
SP - 3028
EP - 3036
JO - Diabetes
JF - Diabetes
IS - 8
ER -