Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus

• Published in: Nature communications 2021-12, Vol.12 (1), p.7173-18, Article 7173
• Main Authors: Tin, Adrienne, 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, 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, Loh, Marie, Snieder, Harold, Waldenberger, Melanie, Levy, Daniel, Woodward, Owen M., Susztak, Katalin, Teumer, Alexander, Köttgen, Anna
• Format: Article
• Language: English
• Subjects: 38/61; 49/61; 631/208/177; 692/308/174; 692/308/575; 692/699/2743; Amino Acid Transport System y+ - genetics; Blood; Cohort Studies; CpG Islands; Deoxyribonucleic acid; DNA; DNA Methylation; Epigenetics; Epigenome; Female; Gene expression; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Glucose Transport Proteins, Facilitative - genetics; Glucose Transport Proteins, Facilitative - metabolism; Gout; Gout - blood; Gout - genetics; Health risks; Humanities and Social Sciences; Humans; Lead poisoning; Loci; Male; Medicin och hälsovetenskap; Metabolic disorders; Metabolic syndrome; multidisciplinary; Risk analysis; Risk factors; Science; Science (multidisciplinary); Uric acid; Uric Acid - blood
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-27198-4

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