PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Exami...

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Tipo de recurso:
Fecha de publicación:
2018
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/20449
Acceso en línea:
https://repository.urosario.edu.co/handle/10336/20449
Palabra clave:
Ion Channel
Transcription Factor
Disequilibrium
Genetic Analysis
Genome
Meta-Analysis
Risk Factor
African
Atrial Fibrillation
Atrioventricular Conduction
Cell Junction
Electric Activity
European
Gene Linkage Disequilibrium
Gene Locus
Genome-Wide Association Study
Heart Block
Heart Depolarization
Heart Rate
Human
Missense Mutation
Phenotype
Pr Interval
Qrs Interval
Signal Transduction
Canal de iones
Factor de transcripción
Sangre
Sistema cardiovascular
Enfermedades
Cardiovascular system
Blood
Heart Disease
Article
Enfermedades cardiovasculares
Fibrilación auricular
Bloqueo cardíaco
Rights
License
Abierto (Texto Completo)
id EDOCUR2_72cd09d329b8429fcdd035a3bf6d9a49
oai_identifier_str oai:repository.urosario.edu.co:10336/20449
network_acronym_str EDOCUR2
network_name_str Repositorio EdocUR - U. Rosario
repository_id_str
dc.title.spa.fl_str_mv PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
title PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
spellingShingle PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
Gudnason, Vilmundur
Ion Channel
Transcription Factor
Disequilibrium
Genetic Analysis
Genome
Meta-Analysis
Risk Factor
African
Atrial Fibrillation
Atrioventricular Conduction
Cell Junction
Electric Activity
European
Gene Linkage Disequilibrium
Gene Locus
Genome-Wide Association Study
Heart Block
Heart Depolarization
Heart Rate
Human
Missense Mutation
Phenotype
Pr Interval
Qrs Interval
Signal Transduction
Canal de iones
Factor de transcripción
Sangre
Sistema cardiovascular
Enfermedades
Cardiovascular system
Blood
Heart Disease
Article
Enfermedades cardiovasculares
Fibrilación auricular
Bloqueo cardíaco
title_short PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
title_full PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
title_fullStr PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
title_full_unstemmed PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
title_sort PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity
dc.creator.none.fl_str_mv Gudnason, Vilmundur
Hayward, Caroline
Heckbert, Susan R.
Hicks, Andrew A.
Jukema, J. Wouter
Kääb, Stefan
Lehtimäk, Terho
Liu, Yongmei
Munroe, Patricia B.
Parsa, Afshin
Polasek, Ozren
Psaty, Bruce M.
Roden, Dan M.
Schnabel, Renate B.
Sinagra, Gianfranco
Stefansson, Kari
Stricker, Bruno H.
Harst, Pim van der
Duijn, Cornelia M. van
Wilson, James F.
Gharib, Sina A.
Bakker, Paul I.W. de
Isaacs, Aaron
Arking, Dan E.
Sotoodehnia, Nona
dc.creator.google.spa.fl_str_mv van Setten, Jessica
Brody, Jennifer A.
Jamshidi, Yalda
Swenson, Brenton R.
Butler, Anne M.
Campbell, Harry
Del Greco, Fabiola M.
Evans, Daniel S.
Gibson, Quince
Gudbjartsson, Daniel F.
Kerr, Kathleen F.
Krijthe, Bouwe P.
Lyytikäinen, Leo-Pekka
Müller, Christian
Müller-Nurasyid, Martina
Nolte, Ilja M.
Padmanabhan, Sandosh
Ritchie, Marylyn D.
Robino, Antonietta
Smith, Albert V.
Steri, Maristella
Tanaka, Toshiko
Teumer, Alexander
Trompet, Stella
Ulivi, Sheila
Verweij, Niek
Yin, Xiaoyan
Arnar, David O.
Asselbergs, Folkert W.
Bader, Joel S.
Barnard, John
Bis, Josh
Blankenberg, Stefan
Boerwinkle, Eric
Bradford, Yuki
Buckley, Brendan M.
Chung, Mina K.
Crawford, Dana
den Hoed, Marcel
Denny, Josh C.
Dominiczak, Anna F.
Ehret, Georg B.
Eijgelsheim, Mark
Ellinor, Patrick T.
Felix, Stephan B.
Franco, Oscar H.
Franke, Lude
Harris, Tamara B.
Holm, Hilma
Ilaria, Gandin
Iorio, Annamaria
Kähönen, Mika
Kolcic, Ivana
Kors, Jan A.
Lakatta, Edward G.
Launer, Lenore J.
Lin, Honghuang
Lin, Henry J.
Loos, Ruth J.F.
Lubitz, Steven A.
Macfarlane, Peter W.
Magnani, Jared W.
Mateo Leach, Irene
Meitinger, Thomas
Mitchell, Braxton D.
Munzel, Thomas
Papanicolaou, George J.
Peters, Annette
Pfeufer, Arne
Pramstaller, Peter P.
Raitakari, Olli T.
Rotter, Jerome I.
Rudan, Igor
Samani, Nilesh J.
Schlessinger, David
Silva Aldana, Claudia T.
Sinner, Moritz F.
Smith, Jonathan D.
Snieder, Harold
Soliman, Elsayed Z.
Spector, Timothy D.
Stott, David J.
Strauch, Konstantin
Tarasov, Kirill V.
Thorsteinsdottir, Unnur
Uitterlinden, Andre G.
Van Wagoner, David R.
Völker, Uwe
Völzke, Henry
Waldenberger, Melanie
Jan Westra, Harm
Wild, Philipp S.
Zeller, Tanja
Alonso, Alvaro
Avery, Christy L.
Bandinelli, Stefania
Benjamin, Emelia J.
Cucca, Francesco
Dörr, Marcus
Ferrucci, Luigi
Gasparini, Paolo
Gudnason, Vilmundur
Hayward, Caroline
Heckbert, Susan R.
Hicks, Andrew A.
Jukema, J. Wouter
Kääb, Stefan
Lehtimäki, Terho
Liu, Yongmei
Munroe, Patricia B.
Parsa, Afshin
Polasek, Ozren
Psaty, Bruce M.
Roden, Dan M.
Schnabel, Renate B.
Sinagra, Gianfranco
Stefansson, Kari
Stricker, Bruno H.
van der Harst, Pim
van Duijn, Cornelia M.
Wilson,James F.
Gharib, Sina A.
de Bakker, Paul I.W.
Isaacs, Aaron
Arking, Dan E.
Sotoodehnia, Nona
author Gudnason, Vilmundur
author_facet Gudnason, Vilmundur
Hayward, Caroline
Heckbert, Susan R.
Hicks, Andrew A.
Jukema, J. Wouter
Kääb, Stefan
Lehtimäk, Terho
Liu, Yongmei
Munroe, Patricia B.
Parsa, Afshin
Polasek, Ozren
Psaty, Bruce M.
Roden, Dan M.
Schnabel, Renate B.
Sinagra, Gianfranco
Stefansson, Kari
Stricker, Bruno H.
Harst, Pim van der
Duijn, Cornelia M. van
Wilson, James F.
Gharib, Sina A.
Bakker, Paul I.W. de
Isaacs, Aaron
Arking, Dan E.
Sotoodehnia, Nona
author_role author
author2 Hayward, Caroline
Heckbert, Susan R.
Hicks, Andrew A.
Jukema, J. Wouter
Kääb, Stefan
Lehtimäk, Terho
Liu, Yongmei
Munroe, Patricia B.
Parsa, Afshin
Polasek, Ozren
Psaty, Bruce M.
Roden, Dan M.
Schnabel, Renate B.
Sinagra, Gianfranco
Stefansson, Kari
Stricker, Bruno H.
Harst, Pim van der
Duijn, Cornelia M. van
Wilson, James F.
Gharib, Sina A.
Bakker, Paul I.W. de
Isaacs, Aaron
Arking, Dan E.
Sotoodehnia, Nona
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.spa.fl_str_mv Ion Channel
Transcription Factor
Disequilibrium
Genetic Analysis
Genome
Meta-Analysis
Risk Factor
African
Atrial Fibrillation
Atrioventricular Conduction
Cell Junction
Electric Activity
European
Gene Linkage Disequilibrium
Gene Locus
Genome-Wide Association Study
Heart Block
Heart Depolarization
Heart Rate
Human
Missense Mutation
Phenotype
Pr Interval
Qrs Interval
Signal Transduction
Canal de iones
Factor de transcripción
Sangre
Sistema cardiovascular
topic Ion Channel
Transcription Factor
Disequilibrium
Genetic Analysis
Genome
Meta-Analysis
Risk Factor
African
Atrial Fibrillation
Atrioventricular Conduction
Cell Junction
Electric Activity
European
Gene Linkage Disequilibrium
Gene Locus
Genome-Wide Association Study
Heart Block
Heart Depolarization
Heart Rate
Human
Missense Mutation
Phenotype
Pr Interval
Qrs Interval
Signal Transduction
Canal de iones
Factor de transcripción
Sangre
Sistema cardiovascular
Enfermedades
Cardiovascular system
Blood
Heart Disease
Article
Enfermedades cardiovasculares
Fibrilación auricular
Bloqueo cardíaco
dc.subject.ddc.spa.fl_str_mv Enfermedades
dc.subject.keyword.spa.fl_str_mv Cardiovascular system
Blood
Heart Disease
Article
dc.subject.lemb.spa.fl_str_mv Enfermedades cardiovasculares
Fibrilación auricular
Bloqueo cardíaco
description Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development. © 2018, The Author(s).
publishDate 2018
dc.date.created.none.fl_str_mv 2018
dc.date.issued.none.fl_str_mv 2018
dc.date.accessioned.none.fl_str_mv 2019-10-17T12:55:20Z
dc.date.available.none.fl_str_mv 2019-10-17T12:55:20Z
dc.type.eng.fl_str_mv article
dc.type.coarversion.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_6501
dc.type.spa.spa.fl_str_mv Artículo
dc.identifier.doi.none.fl_str_mv 10.1038/s41467-018-04766-9
dc.identifier.issn.none.fl_str_mv 2041-1723
dc.identifier.uri.none.fl_str_mv https://repository.urosario.edu.co/handle/10336/20449
identifier_str_mv 10.1038/s41467-018-04766-9
2041-1723
url https://repository.urosario.edu.co/handle/10336/20449
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.citationTitle.none.fl_str_mv Nature Communications
dc.relation.citationVolume.none.fl_str_mv Vol. 9
dc.relation.ispartof.spa.fl_str_mv Nature Communications, ISSN:2041-1723, Vol. 9 (2018)
dc.relation.uri.spa.fl_str_mv https://www.nature.com/articles/s41467-018-04766-9
dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_abf2
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rights_invalid_str_mv Abierto (Texto Completo)
http://purl.org/coar/access_right/c_abf2
dc.format.mimetype.none.fl_str_mv application/pdf
institution Universidad del Rosario
dc.source.bibliographicCitation.spa.fl_str_mv Kannel, W.B., Benjamin, E.J., Current perceptions of the epidemiology of atrial fibrillation (2009) Cardiol. Clin., 27, pp. 13-24. , PID: 19111760
dc.source.instname.none.fl_str_mv instname:Universidad del Rosario
dc.source.reponame.none.fl_str_mv reponame:Repositorio Institucional EdocUR
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Wouter3eed8533-9017-446a-ae86-947faca0b377600Kääb, Stefana9ccb84b-48aa-441a-a447-f3bbfd643679600Lehtimäk, Terho555e57ed-2a56-4717-a308-7c21515e9ab6600Liu, Yongmei564df5a7-e90d-48a8-9a8d-c27807035466600Munroe, Patricia B.719a0e55-dfbe-40bc-ac8f-d3d788c1d50a600Parsa, Afshin69d37949-e982-4a71-b0e2-a13e2bc84d5b600Polasek, Ozrenfcc0a90c-b65b-4ed6-b83d-9eb892fe6935600Psaty, Bruce M.6af29e96-f6da-438f-a5de-3008df20548e600Roden, Dan M.1e8b9a9d-f537-46b0-9b55-5d84058445d5600Schnabel, Renate B.795f95f4-bf39-4337-ae3d-290fa95af233600Sinagra, Gianfranco885ded04-5178-4e27-a504-bce59bb3a8e8600Stefansson, Karid8ac141b-5a73-4d97-82a0-4710bd052f66600Stricker, Bruno H.a99d6cf2-1da8-48e2-9e93-c3d2e6242f5d600Harst, Pim van der8ecd2d62-eabd-444d-b5a4-f33584312ecf600Duijn, Cornelia M. vandf25179c-f919-49cf-8e1a-c4b86fc5515e600Wilson, James F.3e1d8399-f575-4eb2-99a5-efe7ec8d7ae1600Gharib, Sina A.2603c2e0-affb-4af7-bdda-9464eaefad31600Bakker, Paul I.W. de62203196-e177-47c8-9064-8c6fd6eaaba2600Isaacs, Aarona973d5a7-cb60-4a89-8167-f2811c5918b3600Arking, Dan E.5f3e7585-be94-4fac-bb4d-31c8cf33820a600Sotoodehnia, Nona58cf5ad5-b44e-4c46-b480-0b78cce9775a600van Setten, JessicaBrody, Jennifer A.Jamshidi, YaldaSwenson, Brenton R.Butler, Anne M.Campbell, HarryDel Greco, Fabiola M.Evans, Daniel S.Gibson, QuinceGudbjartsson, Daniel F.Kerr, Kathleen F.Krijthe, Bouwe P.Lyytikäinen, Leo-PekkaMüller, ChristianMüller-Nurasyid, MartinaNolte, Ilja M.Padmanabhan, SandoshRitchie, Marylyn D.Robino, AntoniettaSmith, Albert V.Steri, MaristellaTanaka, ToshikoTeumer, AlexanderTrompet, StellaUlivi, SheilaVerweij, NiekYin, XiaoyanArnar, David O.Asselbergs, Folkert W.Bader, Joel S.Barnard, JohnBis, JoshBlankenberg, StefanBoerwinkle, EricBradford, YukiBuckley, Brendan M.Chung, Mina K.Crawford, Danaden Hoed, MarcelDenny, Josh C.Dominiczak, Anna F.Ehret, Georg B.Eijgelsheim, MarkEllinor, Patrick T.Felix, Stephan B.Franco, Oscar H.Franke, LudeHarris, Tamara B.Holm, HilmaIlaria, GandinIorio, AnnamariaKähönen, MikaKolcic, IvanaKors, Jan A.Lakatta, Edward G.Launer, Lenore J.Lin, HonghuangLin, Henry J.Loos, Ruth J.F.Lubitz, Steven A.Macfarlane, Peter W.Magnani, Jared W.Mateo Leach, IreneMeitinger, ThomasMitchell, Braxton D.Munzel, ThomasPapanicolaou, George J.Peters, AnnettePfeufer, ArnePramstaller, Peter P.Raitakari, Olli T.Rotter, Jerome I.Rudan, IgorSamani, Nilesh J.Schlessinger, DavidSilva Aldana, Claudia T.Sinner, Moritz F.Smith, Jonathan D.Snieder, HaroldSoliman, Elsayed Z.Spector, Timothy D.Stott, David J.Strauch, KonstantinTarasov, Kirill V.Thorsteinsdottir, UnnurUitterlinden, Andre G.Van Wagoner, David R.Völker, UweVölzke, HenryWaldenberger, MelanieJan Westra, HarmWild, Philipp S.Zeller, TanjaAlonso, AlvaroAvery, Christy L.Bandinelli, StefaniaBenjamin, Emelia J.Cucca, FrancescoDörr, MarcusFerrucci, LuigiGasparini, PaoloGudnason, VilmundurHayward, CarolineHeckbert, Susan R.Hicks, Andrew A.Jukema, J. WouterKääb, StefanLehtimäki, TerhoLiu, YongmeiMunroe, Patricia B.Parsa, AfshinPolasek, OzrenPsaty, Bruce M.Roden, Dan M.Schnabel, Renate B.Sinagra, GianfrancoStefansson, KariStricker, Bruno H.van der Harst, Pimvan Duijn, Cornelia M.Wilson,James F.Gharib, Sina A.de Bakker, Paul I.W.Isaacs, AaronArking, Dan E.Sotoodehnia, Nona2019-10-17T12:55:20Z2019-10-17T12:55:20Z20182018Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development. © 2018, The Author(s).application/pdf10.1038/s41467-018-04766-92041-1723https://repository.urosario.edu.co/handle/10336/20449engNature CommunicationsVol. 9Nature Communications, ISSN:2041-1723, Vol. 9 (2018)https://www.nature.com/articles/s41467-018-04766-9Abierto (Texto Completo)http://purl.org/coar/access_right/c_abf2Kannel, W.B., Benjamin, E.J., Current perceptions of the epidemiology of atrial fibrillation (2009) Cardiol. Clin., 27, pp. 13-24. , PID: 19111760instname:Universidad del Rosarioreponame:Repositorio Institucional EdocURIon ChannelTranscription FactorDisequilibriumGenetic AnalysisGenomeMeta-AnalysisRisk FactorAfricanAtrial FibrillationAtrioventricular ConductionCell JunctionElectric ActivityEuropeanGene Linkage DisequilibriumGene LocusGenome-Wide Association StudyHeart BlockHeart DepolarizationHeart RateHumanMissense MutationPhenotypePr IntervalQrs IntervalSignal TransductionCanal de ionesFactor de transcripciónSangreSistema cardiovascularEnfermedades616600Cardiovascular systemBloodHeart DiseaseArticleEnfermedades cardiovascularesFibrilación auricularBloqueo cardíacoPR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activityarticleArtículohttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501van Setten, JessicaBrody, Jennifer A.Jamshidi, YaldaSwenson, Brenton R.Butler, Anne M.Campbell, HarryDel Greco, Fabiola M.Evans, Daniel S.Gibson, QuinceGudbjartsson, Daniel F.Kerr, KathleenKrijthe, Bouwe P.Lyytikäinen, Leo-PekkaMüller, ChristianMüller-Nurasyid, MartinaNolte, Ilja M.Padmanabhan, SandoshRitchie, Marylyn D.Robino, AntoniettaSmith, Albert V.Steri, MaristellaTanaka, ToshikoTeumer, AlexanderTrompet, StellaUlivi, SheilaVerweij, NiekYin, XiaoyanArnar, David O.Asselbergs, Folkert W.Bader, Joel S.Barnard, JohnBis, JoshBlankenberg, StefanBoerwinkle, EricBradford, YukiBuckley, Brendan M.Chung, Mina K.Crawford, Danaden Hoed, MarcelDenny, Josh C.Dominiczak, Anna F.Ehret, Georg B.Eijgelsheim, MarkEllinor, Patrick T.Felix, Stephan B.Franco, Oscar H.Franke, LudeHarris, Tamara B.Holm, HilmaGANDIN, ILARIAIorio, AnnamariaKähönen, MikaKolcic, IvanaKors, Jan A.Lakatta, Edward G.Launer, Lenore J.Lin, HonghuangLin, Henry J.Loos, Ruth J.F.Lubitz, Steven A.Macfarlane, Peter W.Magnani, Jared W.Mateo Leach, IreneMeitinger, ThomasMitchell, Braxton D.Munzel, ThomasPapanicolaou, George J.Peters, AnnettePfeufer, ArnePramstaller, Peter P.Raitakari, Olli T.Rotter, Jerome I.Rudan, IgorSamani, Nilesh J.Schlessinger, DavidSilva Aldana, Claudia T.Sinner, Moritz F.Smith, Jonathan D.Snieder, HaroldSoliman, Elsayed Z.Spector, Timothy D.Stott, David J.Strauch, KonstantinTarasov, Kirill V.Thorsteinsdottir, UnnurUitterlinden, Andre G.Van Wagoner, David R.Völker, UweVölzke, HenryWaldenberger, MelanieWestra, Harm JanWild, Philipp S.Zeller, TanjaAlonso, AlvaroAvery, Christy L.Bandinelli, StefaniaBenjamin, Emelia J.Cucca, FrancescoDörr, MarcusFerrucci, LuigiGasparini, PaoloORIGINAL9.pdfapplication/pdf2370431https://repository.urosario.edu.co/bitstreams/0ada85e2-8e62-456b-b091-097f0cbc3609/downloade8213d40cd6045670bfa1d708db82d84MD51TEXT9.pdf.txt9.pdf.txtExtracted texttext/plain81885https://repository.urosario.edu.co/bitstreams/e894ea83-cb08-4dbc-9e1f-d0cdce66fbed/download66eabe1e32de57ed49ef86e740dadcc6MD52THUMBNAIL9.pdf.jpg9.pdf.jpgGenerated Thumbnailimage/jpeg3303https://repository.urosario.edu.co/bitstreams/5d89c5fd-f515-4b92-a3a0-8ba530e1bad0/download640af909f5d8c764761068639f3843cbMD5310336/20449oai:repository.urosario.edu.co:10336/204492020-02-12 16:21:11.472https://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.co