Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels
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Tin, Adrienne
Marten, Jonathan
Halperin Kuhns, Victoria L.
Li, Yong
Wuttke, Matthias
Kirsten, Holger
Sieber, Karsten B.
Qiu, Chengxiang
Gorski, Mathias
Yu, Zhi
Giri, Ayush
Sveinbjornsson, Gardar
Li, Man
Chu, Audrey Y.
Hoppmann, Anselm
Prins, Bram
Nutile, Teresa
Noce, Damia
Akiyama, Masato
Cocca, Massimiliano
Ghasemi, Sahar
van der Most, Peter J.
Horn, Katrin
Xu, Yizhe
Fuchsberger, Christian
Sedaghat, Sanaz
Afaq, Saima
Amin, Najaf
Ärnlöv, Johan
Bakker, Stephan J. L.
Bansal, Nisha
Baptista, Daniela
Bergmann, Sven
Biggs, Mary L.
Biino, Ginevra
Boerwinkle, Eric
Bottinger, Erwin P.
Boutin, Thibaud S.
Brumat, Marco
Burkhardt, Ralph
Campana, Eric
Campbell, Archie
Campbell, Harry
Carroll, Robert J.
Catamo, Eulalia
Chambers, John C.
Ciullo, Marina
Concas, Maria Pina
Coresh, Josef
Corre, Tanguy
Cusi, Daniele
Felicita, Sala Cinzia
de Borst, Martin H.
De Grandi, Alessandro
de Mutsert, Renée
de Vries, Aiko P. J.
Delgado, Graciela
Demirkan, Ayşe
Devuyst, Olivier
Dittrich, Katalin
Eckardt, Kai-Uwe
Ehret, Georg
Endlich, Karlhans
Evans, Michele K.
Gansevoort, Ron T.
Gasparini, Paolo
Giedraitis, Vilmantas
Gieger, Christian
Girotto, Giorgia
Gögele, Martin
Gordon, Scott D.
Gudbjartsson, Daniel F.
Gudnason, Vilmundur
Haller, Toomas
Hamet, Pavel
Harris, Tamara B.
Hayward, Caroline
Hicks, Andrew A.
Hofer, Edith
Holm, Hilma
Huang, Wei
Hutri-Kähönen, Nina
Hwang, Shih-Jen
Ikram, M. Arfan
Lewis, Raychel M.
Ingelsson, Erik
Jakobsdottir, Johanna
Jonsdottir, Ingileif
Jonsson, Helgi
Joshi, Peter K.
Josyula, Navya Shilpa
Jung, Bettina
Kähönen, Mika
Kamatani, Yoichiro
Kerr, Shona M.
Kiess, Wieland
Kleber, Marcus E.
Koenig, Wolfgang
Kooner, Jaspal S.
Körner, Antje
Kovacs, Peter
Krämer, Bernhard K.
Kronenberg, Florian
Kubo, Michiaki
Kühnel, Brigitte
La Bianca, Martina
Lange, Leslie A.
Lehne, Benjamin
Lehtimäki, Terho
Liu, Jun
Loeffler, Markus
Loos, Ruth J. F.
Lyytikäinen, Leo-Pekka
Magi, Reedik
Mahajan, Anubha
Martin, Nicholas G.
März, Winfried
Mascalzoni, Deborah
Matsuda, Koichi
Meisinger, Christa
Meitinger, Thomas
Metspalu, Andres
Milaneschi, Yuri
Wilson, Otis D.
Mishra, Pashupati P.
Mohlke, Karen L.
Mononen, Nina
Montgomery, Grant W.
Mook-Kanamori, Dennis O.
Müller-Nurasyid, Martina
Nadkarni, Girish N.
Nalls, Mike A.
Nauck, Matthias
Nikus, Kjell
Ning, Boting
Nolte, Ilja M.
Noordam, Raymond
O’Connell, Jeffrey R.
Olafsson, Isleifur
Padmanabhan, Sandosh
Penninx, Brenda W. J. H.
Perls, Thomas
Peters, Annette
Pirastu, Mario
Pirastu, Nicola
Pistis, Giorgio
Polasek, Ozren
Ponte, Belen
Porteous, David J.
Poulain, Tanja
Preuss, Michael H.
Rabelink, Ton J.
Raffield, Laura M.
Raitakari, Olli T.
Rettig, Rainer
Rheinberger, Myriam
Rice, Kenneth M.
Rizzi, Federica
Robino, Antonietta
Rudan, Igor
Krajcoviechova, Alena
Cifkova, Renata
Rueedi, Rico
Ruggiero, Daniela
Ryan, Kathleen A.
Saba, Yasaman
Salvi, Erika
Schmidt, Helena
Schmidt, Reinhold
Shaffer, Christian M.
Smith, Albert V.
Smith, Blair H.
Spracklen, Cassandra N.
Strauch, Konstantin
Stumvoll, Michael
Sulem, Patrick
Tajuddin, Salman M.
Teren, Andrej
Thiery, Joachim
Thio, Chris H. L.
Thorsteinsdottir, Unnur
Toniolo, Daniela
Tönjes, Anke
Tremblay, Johanne
Uitterlinden, André G.
Vaccargiu, Simona
van der Harst, Pim
van Duijn, Cornelia M.
Verweij, Niek
Völker, Uwe
Vollenweider, Peter
Waeber, Gerard
Waldenberger, Melanie
Whitfield, John B.
Wild, Sarah H.
Wilson, James F.
Yang, Qiong
Zhang, Weihua
Zonderman, Alan B.
Bochud, Murielle
Wilson, James G.
Pendergrass, Sarah A.
Ho, Kevin
Parsa, Afshin
Pramstaller, Peter P.
Psaty, Bruce M.
Böger, Carsten A.
Snieder, Harold
Butterworth, Adam S.
Okada, Yukinori
Edwards, Todd L.
Stefansson, Kari
Susztak, Katalin
Scholz, Markus
Heid, Iris M.
Hung, Adriana M.
Teumer, Alexander
Pattaro, Cristian
Woodward, Owen M.
Vitart, Veronique
Köttgen, Anna
Published Version
https://doi.org/10.1038/s41588-019-0504-xMetadata
Show full item recordCitation
Tin, Adrienne, Jonathan Marten, Victoria L. Halperin Kuhns, Yong Li, Matthias Wuttke, Holger Kirsten, Karsten B. Sieber et al. "Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels." Nat Genet 51, no. 10 (2019): 1459-1474. DOI: 10.1038/s41588-019-0504-xAbstract
Elevated serum urate levels cause gout and correlate with cardio-metabolic diseases via poorly understood mechanisms. We performed a trans-ethnic genome-wide association study of serum urate among 457,690 individuals, identifying 183 loci (147 novel) that improve prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardio-metabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci, and co-localization with gene expression in 47 tissues implicated kidney and liver as main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A trans-activated the promoter of the major urate transporter ABCG2 in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional co-regulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardio-metabolic traits.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858555/Citable link to this page
https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37368611
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