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Nature genetics · 2019

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

СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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, O'Connor Luke J, 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, German Chronic Kidney Disease Study, 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, Kanai Masahiro, 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, Lifelines Cohort Study, 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, V. A. Million Veteran Program, O'Donnell Christopher J, Wilson Otis D, Gaziano J Michael, 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

Аннотация

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты