Show simple item record

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels

dc.contributor.authorTin, Adrienne
dc.contributor.authorMarten, Jonathan
dc.contributor.authorHalperin Kuhns, Victoria L.
dc.contributor.authorLi, Yong
dc.contributor.authorWuttke, Matthias
dc.contributor.authorKirsten, Holger
dc.contributor.authorSieber, Karsten B.
dc.contributor.authorQiu, Chengxiang
dc.contributor.authorGorski, Mathias
dc.contributor.authorYu, Zhi
dc.contributor.authorGiri, Ayush
dc.contributor.authorSveinbjornsson, Gardar
dc.contributor.authorLi, Man
dc.contributor.authorChu, Audrey Y.
dc.contributor.authorHoppmann, Anselm
dc.contributor.authorO'Connor, Luke
dc.contributor.authorPrins, Bram
dc.contributor.authorNutile, Teresa
dc.contributor.authorNoce, Damia
dc.contributor.authorAkiyama, Masato
dc.contributor.authorCocca, Massimiliano
dc.contributor.authorGhasemi, Sahar
dc.contributor.authorvan der Most, Peter J.
dc.contributor.authorHorn, Katrin
dc.contributor.authorXu, Yizhe
dc.contributor.authorFuchsberger, Christian
dc.contributor.authorSedaghat, Sanaz
dc.contributor.authorAfaq, Saima
dc.contributor.authorAmin, Najaf
dc.contributor.authorÄrnlöv, Johan
dc.contributor.authorBakker, Stephan J. L.
dc.contributor.authorBansal, Nisha
dc.contributor.authorBaptista, Daniela
dc.contributor.authorBergmann, Sven
dc.contributor.authorBiggs, Mary L.
dc.contributor.authorBiino, Ginevra
dc.contributor.authorBoerwinkle, Eric
dc.contributor.authorBottinger, Erwin P.
dc.contributor.authorBoutin, Thibaud S.
dc.contributor.authorBrumat, Marco
dc.contributor.authorBurkhardt, Ralph
dc.contributor.authorCampana, Eric
dc.contributor.authorCampbell, Archie
dc.contributor.authorCampbell, Harry
dc.contributor.authorCarroll, Robert J.
dc.contributor.authorCatamo, Eulalia
dc.contributor.authorChambers, John C.
dc.contributor.authorCiullo, Marina
dc.contributor.authorConcas, Maria Pina
dc.contributor.authorCoresh, Josef
dc.contributor.authorCorre, Tanguy
dc.contributor.authorCusi, Daniele
dc.contributor.authorFelicita, Sala Cinzia
dc.contributor.authorde Borst, Martin H.
dc.contributor.authorDe Grandi, Alessandro
dc.contributor.authorde Mutsert, Renée
dc.contributor.authorde Vries, Aiko P. J.
dc.contributor.authorDelgado, Graciela
dc.contributor.authorDemirkan, Ayşe
dc.contributor.authorDevuyst, Olivier
dc.contributor.authorDittrich, Katalin
dc.contributor.authorEckardt, Kai-Uwe
dc.contributor.authorEhret, Georg
dc.contributor.authorEndlich, Karlhans
dc.contributor.authorEvans, Michele K.
dc.contributor.authorGansevoort, Ron T.
dc.contributor.authorGasparini, Paolo
dc.contributor.authorGiedraitis, Vilmantas
dc.contributor.authorGieger, Christian
dc.contributor.authorGirotto, Giorgia
dc.contributor.authorGögele, Martin
dc.contributor.authorGordon, Scott D.
dc.contributor.authorGudbjartsson, Daniel F.
dc.contributor.authorGudnason, Vilmundur
dc.contributor.authorHaller, Toomas
dc.contributor.authorHamet, Pavel
dc.contributor.authorHarris, Tamara B.
dc.contributor.authorHayward, Caroline
dc.contributor.authorHicks, Andrew A.
dc.contributor.authorHofer, Edith
dc.contributor.authorHolm, Hilma
dc.contributor.authorHuang, Wei
dc.contributor.authorHutri-Kähönen, Nina
dc.contributor.authorHwang, Shih-Jen
dc.contributor.authorIkram, M. Arfan
dc.contributor.authorLewis, Raychel M.
dc.contributor.authorIngelsson, Erik
dc.contributor.authorJakobsdottir, Johanna
dc.contributor.authorJonsdottir, Ingileif
dc.contributor.authorJonsson, Helgi
dc.contributor.authorJoshi, Peter K.
dc.contributor.authorJosyula, Navya Shilpa
dc.contributor.authorJung, Bettina
dc.contributor.authorKähönen, Mika
dc.contributor.authorKamatani, Yoichiro
dc.contributor.authorKanai, Masahiro
dc.contributor.authorKerr, Shona M.
dc.contributor.authorKiess, Wieland
dc.contributor.authorKleber, Marcus E.
dc.contributor.authorKoenig, Wolfgang
dc.contributor.authorKooner, Jaspal S.
dc.contributor.authorKörner, Antje
dc.contributor.authorKovacs, Peter
dc.contributor.authorKrämer, Bernhard K.
dc.contributor.authorKronenberg, Florian
dc.contributor.authorKubo, Michiaki
dc.contributor.authorKühnel, Brigitte
dc.contributor.authorLa Bianca, Martina
dc.contributor.authorLange, Leslie A.
dc.contributor.authorLehne, Benjamin
dc.contributor.authorLehtimäki, Terho
dc.contributor.authorLiu, Jun
dc.contributor.authorLoeffler, Markus
dc.contributor.authorLoos, Ruth J. F.
dc.contributor.authorLyytikäinen, Leo-Pekka
dc.contributor.authorMagi, Reedik
dc.contributor.authorMahajan, Anubha
dc.contributor.authorMartin, Nicholas G.
dc.contributor.authorMärz, Winfried
dc.contributor.authorMascalzoni, Deborah
dc.contributor.authorMatsuda, Koichi
dc.contributor.authorMeisinger, Christa
dc.contributor.authorMeitinger, Thomas
dc.contributor.authorMetspalu, Andres
dc.contributor.authorMilaneschi, Yuri
dc.contributor.authorO'Donnell, Christopher
dc.contributor.authorWilson, Otis D.
dc.contributor.authorGaziano, John
dc.contributor.authorMishra, Pashupati P.
dc.contributor.authorMohlke, Karen L.
dc.contributor.authorMononen, Nina
dc.contributor.authorMontgomery, Grant W.
dc.contributor.authorMook-Kanamori, Dennis O.
dc.contributor.authorMüller-Nurasyid, Martina
dc.contributor.authorNadkarni, Girish N.
dc.contributor.authorNalls, Mike A.
dc.contributor.authorNauck, Matthias
dc.contributor.authorNikus, Kjell
dc.contributor.authorNing, Boting
dc.contributor.authorNolte, Ilja M.
dc.contributor.authorNoordam, Raymond
dc.contributor.authorO’Connell, Jeffrey R.
dc.contributor.authorOlafsson, Isleifur
dc.contributor.authorPadmanabhan, Sandosh
dc.contributor.authorPenninx, Brenda W. J. H.
dc.contributor.authorPerls, Thomas
dc.contributor.authorPeters, Annette
dc.contributor.authorPirastu, Mario
dc.contributor.authorPirastu, Nicola
dc.contributor.authorPistis, Giorgio
dc.contributor.authorPolasek, Ozren
dc.contributor.authorPonte, Belen
dc.contributor.authorPorteous, David J.
dc.contributor.authorPoulain, Tanja
dc.contributor.authorPreuss, Michael H.
dc.contributor.authorRabelink, Ton J.
dc.contributor.authorRaffield, Laura M.
dc.contributor.authorRaitakari, Olli T.
dc.contributor.authorRettig, Rainer
dc.contributor.authorRheinberger, Myriam
dc.contributor.authorRice, Kenneth M.
dc.contributor.authorRizzi, Federica
dc.contributor.authorRobino, Antonietta
dc.contributor.authorRudan, Igor
dc.contributor.authorKrajcoviechova, Alena
dc.contributor.authorCifkova, Renata
dc.contributor.authorRueedi, Rico
dc.contributor.authorRuggiero, Daniela
dc.contributor.authorRyan, Kathleen A.
dc.contributor.authorSaba, Yasaman
dc.contributor.authorSalvi, Erika
dc.contributor.authorSchmidt, Helena
dc.contributor.authorSchmidt, Reinhold
dc.contributor.authorShaffer, Christian M.
dc.contributor.authorSmith, Albert V.
dc.contributor.authorSmith, Blair H.
dc.contributor.authorSpracklen, Cassandra N.
dc.contributor.authorStrauch, Konstantin
dc.contributor.authorStumvoll, Michael
dc.contributor.authorSulem, Patrick
dc.contributor.authorTajuddin, Salman M.
dc.contributor.authorTeren, Andrej
dc.contributor.authorThiery, Joachim
dc.contributor.authorThio, Chris H. L.
dc.contributor.authorThorsteinsdottir, Unnur
dc.contributor.authorToniolo, Daniela
dc.contributor.authorTönjes, Anke
dc.contributor.authorTremblay, Johanne
dc.contributor.authorUitterlinden, André G.
dc.contributor.authorVaccargiu, Simona
dc.contributor.authorvan der Harst, Pim
dc.contributor.authorvan Duijn, Cornelia M.
dc.contributor.authorVerweij, Niek
dc.contributor.authorVölker, Uwe
dc.contributor.authorVollenweider, Peter
dc.contributor.authorWaeber, Gerard
dc.contributor.authorWaldenberger, Melanie
dc.contributor.authorWhitfield, John B.
dc.contributor.authorWild, Sarah H.
dc.contributor.authorWilson, James F.
dc.contributor.authorYang, Qiong
dc.contributor.authorZhang, Weihua
dc.contributor.authorZonderman, Alan B.
dc.contributor.authorBochud, Murielle
dc.contributor.authorWilson, James G.
dc.contributor.authorPendergrass, Sarah A.
dc.contributor.authorHo, Kevin
dc.contributor.authorParsa, Afshin
dc.contributor.authorPramstaller, Peter P.
dc.contributor.authorPsaty, Bruce M.
dc.contributor.authorBöger, Carsten A.
dc.contributor.authorSnieder, Harold
dc.contributor.authorButterworth, Adam S.
dc.contributor.authorOkada, Yukinori
dc.contributor.authorEdwards, Todd L.
dc.contributor.authorStefansson, Kari
dc.contributor.authorSusztak, Katalin
dc.contributor.authorScholz, Markus
dc.contributor.authorHeid, Iris M.
dc.contributor.authorHung, Adriana M.
dc.contributor.authorTeumer, Alexander
dc.contributor.authorPattaro, Cristian
dc.contributor.authorWoodward, Owen M.
dc.contributor.authorVitart, Veronique
dc.contributor.authorKöttgen, Anna
dc.date.accessioned2021-07-19T15:26:13Z
dc.date.issued2019-10
dc.identifier.citationTin, 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-x
dc.identifier.issn1061-4036en_US
dc.identifier.issn1546-1718en_US
dc.identifier.urihttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37368611*
dc.description.abstractElevated 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.en_US
dc.language.isoen_USen_US
dc.publisherSpringer Science and Business Media LLCen_US
dc.relationTarget genes, variants, tissues and transcriptional pathways for the regulation of serum urate levels in humansen_US
dc.relation.isversionofdoi:10.1038/s41588-019-0504-xen_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858555/en_US
dash.licenseMETA_ONLY
dc.subjectGeneticsen_US
dc.titleTarget genes, variants, tissues and transcriptional pathways influencing human serum urate levelsen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalNat Geneten_US
dash.depositing.authorO'Connor, Luke
dash.waiver2019-06-25
dc.date.available2021-07-19T15:26:13Z
dash.affiliation.otherHarvard T.H. Chan School of Public Healthen_US
dc.identifier.doi10.1038/s41588-019-0504-x
dc.source.journalNat Genet
dash.waiver.reasonThis waiver is for a publication in Nature Genetics, on which I am a middle author.en_US
dash.source.volume51en_US
dash.source.page1459-1474en_US
dash.source.issue10en_US
dash.contributor.affiliatedO'Connor, Luke
dash.contributor.affiliatedKanai, Masahiro
dash.contributor.affiliatedO'Donnell, Christopher
dash.contributor.affiliatedGaziano, John


Files in this item

Thumbnail
Name:
urate_submitted_nat_genet_5356 ...
Size:
2.686Mb
Format:
PDF
Description:
Manuscript file
View/Open

This item appears in the following Collection(s)

Show simple item record