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Title: Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus
Authors: Tin, Adrienne
Schlosser, Pascal
Matias-Garcia, Pamela R.
Thio, Chris H. L.
Joehanes, Roby
Liu, Hongbo
Yu, Zhi
Weihs, Antoine
Hoppmann, Anselm
Grundner-Culemann, Franziska
Min, Josine L.
Kuhns, Victoria L. Halperin
Adeyemo, Adebowale A.
Agyemang, Charles
Ärnlöv, Johan
Aziz, Nasir A.
Baccarelli, Andrea
Bochud, Murielle
Brenner, Hermann
Bressler, Jan
Breteler, Monique M. B.
Carmeli, Cristian
Chaker, Layal
Coresh, Josef
Corre, Tanguy
Correa, Adolfo
Cox, Simon R.
Delgado, Graciela E.
Eckardt, Kai-Uwe
Ekici, Arif B.
Endlich, Karlhans
Floyd, James S.
Fraszczyk, Eliza
Gao, Xu
Gào, Xīn
Gelber, Allan C.
Ghanbari, Mohsen
Ghasemi, Sahar
Gieger, Christian
Greenland, Philip
Grove, Megan L.
Harris, Sarah E.
Hemani, Gibran
Henneman, Peter
Herder, Christian
Horvath, Steve
Hou, Lifang
Hurme, Mikko A.
Hwang, Shih-Jen
Kardia, Sharon L. R.
Kasela, Silva
Kleber, Marcus E.
Koenig, Wolfgang
Kooner, Jaspal S.
Kronenberg, Florian
Kühnel, Brigitte
Ladd-Acosta, Christine
Lehtimäki, Terho
Lind, Lars
Liu, Dan
Lloyd-Jones, Donald M.
Lorkowski, Stefan
Lu, Ake T.
Marioni, Riccardo E.
März, Winfried
McCartney, Daniel L.
Meeks, Karlijn A. C.
Milani, Lili
Mishra, Pashupati P.
Nauck, Matthias
Nowak, Christoph
Peters, Annette
Prokisch, Holger
Psaty, Bruce M.
Raitakari, Olli T.
Ratliff, Scott M.
Reiner, Alex P.
Schöttker, Ben
Schwartz, Joel
Sedaghat, Sanaz
Smith, Jennifer A.
Sotoodehnia, Nona
Stocker, Hannah R.
Stringhini, Silvia
Sundström, Johan
Swenson, Brenton R.
van Meurs, Joyce B. J.
van Vliet-Ostaptchouk, Jana V.
Venema, Andrea
Völker, Uwe
Winkelmann, Juliane
Wolffenbuttel, Bruce H. R.
Zhao, Wei
Zheng, Yinan
Milani, Lili
Esko, Tõnu
Metspalu, Andres
Mägi, Reedik
Nelis, Mari
Min, Josine L.
Hemani, Gibran
Loh, Marie
Snieder, Harold
Waldenberger, Melanie
Levy, Daniel
Akilesh, Shreeram
Woodward, Owen M.
Susztak, Katalin
Teumer, Alexander
Köttgen, Anna
Keywords: Science::Medicine
Issue Date: 2021
Source: Tin, A., Schlosser, P., Matias-Garcia, P. R., Thio, C. H. L., Joehanes, R., Liu, H., Yu, Z., Weihs, A., Hoppmann, A., Grundner-Culemann, F., Min, J. L., Kuhns, V. L. H., Adeyemo, A. A., Agyemang, C., Ärnlöv, J., Aziz, N. A., Baccarelli, A., Bochud, M., Brenner, H., ...Köttgen, A. (2021). Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus. Nature Communications, 12(1), 7173-.
Project: NMRC/STaR/0028/2017
Journal: Nature Communications
Abstract: Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate (discovery, n = 12,474, replication, n = 5522). The 100 replicated, epigenome-wide significant (p < 1.1E-7) CpGs explain 11.6% of the serum urate variance. At SLC2A9, the serum urate locus with the largest effect in genome-wide association studies (GWAS), five CpGs are associated with SLC2A9 gene expression. Four CpGs at SLC2A9 have significant causal effects on serum urate levels and/or gout, and two of these partly mediate the effects of urate-associated GWAS variants. In other genes, including SLC7A11 and PHGDH, 17 urate-associated CpGs are associated with conditions defining metabolic syndrome, suggesting that these CpGs may represent a blood DNA methylation signature of cardiometabolic risk factors. This study demonstrates that EWAS can provide new insights into GWAS loci and the correlation of serum urate with other complex traits.
ISSN: 2041-1723
DOI: 10.1038/s41467-021-27198-4
Rights: © The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit licenses/by/4.0/.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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