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dc.contributor.authorTin, Adrienne
dc.contributor.authorSchlosser, Pascal
dc.contributor.authorMatias-Garcia, Pamela R
dc.contributor.authorThio, Chris H L
dc.contributor.authorJoehanes, Roby
dc.contributor.authorLiu, Hongbo
dc.contributor.authorYu, Zhi
dc.contributor.authorWeihs, Antoine
dc.contributor.authorHoppmann, Anselm
dc.contributor.authorGrundner-Culemann, Franziska
dc.contributor.authorMin, Josine L
dc.contributor.authorKuhns, Victoria L Halperin
dc.contributor.authorAdeyemo, Adebowale A
dc.contributor.authorAgyemang, Charles
dc.contributor.authorÄrnlöv, Johan
dc.contributor.authorAziz, Nasir A
dc.contributor.authorBaccarelli, Andrea
dc.contributor.authorBochud, Murielle
dc.contributor.authorBrenner, Hermann
dc.contributor.authorBressler, Jan
dc.contributor.authorBreteler, Monique M B
dc.contributor.authorCarmeli, Cristian
dc.contributor.authorChaker, Layal
dc.contributor.authorCoresh, Josef
dc.contributor.authorCorre, Tanguy
dc.contributor.authorCorrea, Adolfo
dc.contributor.authorCox, Simon R
dc.contributor.authorDelgado, Graciela E
dc.contributor.authorEckardt, Kai-Uwe
dc.contributor.authorEkici, Arif B
dc.contributor.authorEndlich, Karlhans
dc.contributor.authorFloyd, James S
dc.contributor.authorFraszczyk, Eliza
dc.contributor.authorGao, Xu
dc.contributor.authorGào, Xīn
dc.contributor.authorGelber, Allan C
dc.contributor.authorGhanbari, Mohsen
dc.contributor.authorGhasemi, Sahar
dc.contributor.authorGieger, Christian
dc.contributor.authorGreenland, Philip
dc.contributor.authorGrove, Megan L
dc.contributor.authorHarris, Sarah E
dc.contributor.authorHemani, Gibran
dc.contributor.authorHenneman, Peter
dc.contributor.authorHerder, Christian
dc.contributor.authorHorvath, Steve
dc.contributor.authorHou, Lifang
dc.contributor.authorHurme, Mikko A
dc.contributor.authorHwang, Shih-Jen
dc.contributor.authorKardia, Sharon L R
dc.contributor.authorKasela, Silva
dc.contributor.authorKleber, Marcus E
dc.contributor.authorKoenig, Wolfgang
dc.contributor.authorKooner, Jaspal S
dc.contributor.authorKronenberg, Florian
dc.contributor.authorKühnel, Brigitte
dc.contributor.authorLadd-Acosta, Christine
dc.contributor.authorLehtimäki, Terho
dc.contributor.authorLind, Lars
dc.contributor.authorLiu, Dan
dc.contributor.authorLloyd-Jones, Donald M
dc.contributor.authorLorkowski, Stefan
dc.contributor.authorLu, Ake T
dc.contributor.authorMarioni, Riccardo E
dc.contributor.authorMärz, Winfried
dc.contributor.authorMcCartney, Daniel L
dc.contributor.authorMeeks, Karlijn A C
dc.contributor.authorMilani, Lili
dc.contributor.authorMishra, Pashupati P
dc.contributor.authorNauck, Matthias
dc.contributor.authorNowak, Christoph
dc.contributor.authorPeters, Annette
dc.contributor.authorProkisch, Holger
dc.contributor.authorPsaty, Bruce M
dc.contributor.authorRaitakari, Olli T
dc.contributor.authorRatliff, Scott M
dc.contributor.authorReiner, Alex P
dc.contributor.authorSchöttker, Ben
dc.contributor.authorSchwartz, Joel
dc.contributor.authorSedaghat, Sanaz
dc.contributor.authorSmith, Jennifer A
dc.contributor.authorSotoodehnia, Nona
dc.contributor.authorStocker, Hannah R
dc.contributor.authorStringhini, Silvia
dc.contributor.authorSundström, Johan
dc.contributor.authorSwenson, Brenton R
dc.contributor.authorvan Meurs, Joyce B J
dc.contributor.authorvan Vliet-Ostaptchouk, Jana V
dc.contributor.authorVenema, Andrea
dc.contributor.authorVölker, Uwe
dc.contributor.authorWinkelmann, Juliane
dc.contributor.authorWolffenbuttel, Bruce H R
dc.contributor.authorZhao, Wei
dc.contributor.authorZheng, Yinan
dc.contributor.authorLoh, Marie
dc.contributor.authorSnieder, Harold
dc.contributor.authorWaldenberger, Melanie
dc.contributor.authorLevy, Daniel
dc.contributor.authorAkilesh, Shreeram
dc.contributor.authorWoodward, Owen M
dc.contributor.authorSusztak, Katalin
dc.contributor.authorTeumer, Alexander
dc.contributor.authorKöttgen, Anna
dc.date.accessioned2021-12-16T19:12:12Z
dc.date.available2021-12-16T19:12:12Z
dc.date.issued2021-12-09
dc.identifier.urihttp://hdl.handle.net/10713/17429
dc.description.abstractElevated 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.en_US
dc.description.urihttps://doi.org/10.1038/s41467-021-27198-4en_US
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofNature Communicationsen_US
dc.rights© 2021. The Author(s).en_US
dc.subjectcardiometabolic risk factorsen_US
dc.subjectepigenome-wide association studiesen_US
dc.subjectserum urate levelsen_US
dc.subject.meshDNA Methylationen_US
dc.subject.meshGouten_US
dc.subject.meshUric Aciden_US
dc.titleEpigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locusen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41467-021-27198-4
dc.identifier.pmid34887389
dc.source.volume12
dc.source.issue1
dc.source.beginpage7173
dc.source.endpage
dc.source.countryUnited States
dc.source.countryEngland


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