Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the <em>SLC2A9</em> locus.
- 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.
- Bressler, J.
- Breteler, M.M.B.
- Carmeli, C.
- Chaker, L.
- Coresh, J.
- Corre, T.
- Correa, A.
- Cox, S.R.
- Delgado, G.E.
- Eckardt, K.U.
- Ekici, A.B.
- Endlich, K.
- Floyd, J.S.
- Fraszczyk, E.
- Gao, X.
- Gelber, A.C.
- Ghanbari, M.
- Ghasemi, S.
- Gieger, C.
- Greenland, P.
- Grove, M.L.
- Harris, S.E.
- Hemani, G.
- Henneman, P.
- Herder, C.
- Horvath, S.
- Hou, L.
- Hurme, M.A.
- Hwang, S.J.
- Kardia, S.L.R.
- Kasela, S.
- Kleber, M.E.
- Koenig, W.
- Kooner, J.S.
- Kronenberg, F.
- Kühnel, B.
- Ladd-Acosta, C.
- Lehtimäki, T.
- Lind, L.
- Liu, D.
- Lloyd-Jones, D.M.
- Lorkowski, S.
- Lu, A.T.
- Marioni, R.E.
- März, W.
- McCartney, D.L.
- Meeks, K.A.C.
- Milani, L.
- Mishra, P.P.
- Nauck, M.
- Nowak, C.
- Peters, A.
- Prokisch, H.
- Psaty, B.M.
- Raitakari, O.T.
- Ratliff, S.M.
- Reiner, A.P.
- Schöttker, B.
- Schwartz, J.
- Sedaghat, S.
- Smith, J.A.
- Sotoodehnia, N.
- Stocker, H.R.
- Stringhini, S.
- Sundström, J.
- Swenson, B.R.
- van Meurs, J.B.J.
- van Vliet-Ostaptchouk, J.V.
- Venema, A.
- Völker, U.
- Winkelmann, J.
- Wolffenbuttel, B.H.R.
- Zhao, W.
- Zheng, Y.
- Estonian Biobank Research Team
- Genetics of DNA Methylation Consortium
- Loh, M.
- Snieder, H.
- Waldenberger, M.
- Levy, D.
- Akilesh, S.
- Woodward, O.M.
- Susztak, K.
- Teumer, A.
- Köttgen, A.
DOIAbstract
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 ...
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